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I'm interested in learning about computational modeling in biophysics. I have heard some amount about people modeling proteins as a network of ideal springs to examine things like conformation switching. I was thinking it would be cool to try to make a very simple model of a small motif undergoing denaturation at certain temperatures while being stable at others.
Does anyone know of a good reference about protein modeling that would be understandable to someone who is decent with math/physics/programming but is in no way a mathematician/physicist/computer scientist?
Also, if you have a better idea of a simple project for me to practice computational modeling in biophysics (or even just any biology) I would appreciate hearing it.
Well I sometimes use PDB files from proteins whose structure has been identified and study them. I use swiss PDB viewer software to do this and its pretty neat! I haven't looked at the biophysical data associated with a PDB file but I'm pretty sure they are there since you wouldn't be able to make the calculations and resolve the protein structure and confirmation without that kind of data. All you need is to download the software, go to Uniprot database and use the accession number of a protein you are interested in, see if its structure is resolved and either download the PDB file or use the accession number to download the file inside the software.
Modeling protein conformational transitions by a combination of coarse-grained normal mode analysis and robotics-inspired methods
Obtaining atomic-scale information about large-amplitude conformational transitions in proteins is a challenging problem for both experimental and computational methods. Such information is, however, important for understanding the mechanisms of interaction of many proteins.
This paper presents a computationally efficient approach, combining methods originating from robotics and computational biophysics, to model protein conformational transitions. The ability of normal mode analysis to predict directions of collective, large-amplitude motions is applied to bias the conformational exploration performed by a motion planning algorithm. To reduce the dimension of the problem, normal modes are computed for a coarse-grained elastic network model built on short fragments of three residues. Nevertheless, the validity of intermediate conformations is checked using the all-atom model, which is accurately reconstructed from the coarse-grained one using closed-form inverse kinematics.
Tests on a set of ten proteins demonstrate the ability of the method to model conformational transitions of proteins within a few hours of computing time on a single processor. These results also show that the computing time scales linearly with the protein size, independently of the protein topology. Further experiments on adenylate kinase show that main features of the transition between the open and closed conformations of this protein are well captured in the computed path.
The proposed method enables the simulation of large-amplitude conformational transitions in proteins using very few computational resources. The resulting paths are a first approximation that can directly provide important information on the molecular mechanisms involved in the conformational transition. This approximation can be subsequently refined and analyzed using state-of-the-art energy models and molecular modeling methods.
Post-translational phosphorylation is a ubiquitous mechanism for modulating protein activity and protein-protein interactions. In this work, we examine how phosphorylation can modulate the conformation of a protein by changing the energy landscape. We present a molecular mechanics method in which we phosphorylate proteins in silico and then predict how the conformation of the protein will change in response to phosphorylation. We apply this method to a test set comprised of proteins with both phosphorylated and non-phosphorylated crystal structures, and demonstrate that it is possible to predict localized phosphorylation-induced conformational changes, or the absence of conformational changes, with near-atomic accuracy in most cases. Examples of proteins used for testing our methods include kinases and prokaryotic response regulators. Through a detailed case study of cyclin-dependent kinase 2, we also illustrate how the computational methods can be used to provide new understanding of how phosphorylation drives conformational change, why substituting Glu or Asp for a phosphorylated amino acid does not always mimic the effects of phosphorylation, and how a phosphatase can “capture” a phosphorylated amino acid. This work illustrates how computational methods can be used to elucidate principles and mechanisms of post-translational phosphorylation, which can ultimately help to bridge the gap between the number of known sites of phosphorylation and the number of structures of phosphorylated proteins.
Examples of our methods and research include
Department scientists apply a variety of biophysical methods to detect and analyze the structures, conformational dynamics and interactions of macromolecules such as proteins and nucleic acids (e.g., RNA) as well as small molecules and metabolites. These include:
- X-ray crystallography—to determine atomic-level molecular architecture, including specific active (binding) and/or inactive conformations and the binding of catalytically essential metal ions.
- Small-angle X-ray scattering (SAXS)—x-ray scattering in solution that generates coarser measures of molecular envelopes rather than structural details, thus detecting major changes in conformation.
- Fluorescence resonance energy transfer (FRET)—measures of energy transfer efficiency between two fluorescent labeling compounds (fluorophores) in order to determine distances between them, providing measures of structure and conformational change.
- Nuclear magnetic resonance (NMR) spectroscopy—which sensitively detects flexible macromolecules and structures (e.g., transmembrane proteins, RNA, multi-domain proteins) in solution rather than in a crystallized form, thus capturing them as they cycle through ensembles of conformations (dynamics), in transient interactions with other molecules, and as in vitro confirmation of binding activity and locations in a non-crystallized state.
In addition to providing information on individual proteins and their substructures (domains, active sites), their conformational dynamics, and specific sites of weak/transient interactions, these biophysical methods measure the results of experiments that apply the modern tools of molecular and chemical biology, such as site-directed mutagenesis, enzyme inhibition, and kinetic analysis (e.g., showing how changes in specific residues alter the rate of enzyme catalytic action or determining binding mode of a drug to an allosteric site).
Notably, the department is home to the state-of-the-art UCSF NMR Laboratory, used by department, School, UCSF and qualified outside researchers.
Department-based UCSF Nuclear Magnetic Resonance (NMR) laboratory
NMR spectroscopy resolves molecular function by detecting specific atomic nuclei, such as those of ubiquitous hydrogen atoms, which spin like tops with distinctive wobbles (precessions) when placed in a magnetic field. (NMR spectrometers generate such fields using powerful super-cooled, super conducting magnets.)
Each atom’s rate of precession (frequency) can also be altered not just by the overall magnetic field generated by the spectrometer, but additionally by local fields from the spinning nuclei in adjacent atoms and molecular structures.
NMR spectrum of hexaborane (B6H10) molecule showing peaks shifted in frequency, which give clues to the molecular structure.
When they are subjected to short bursts (pulses) of radio waves, precession frequencies can be detected, amplified, and represented in charts called spectra. A spectrum gives a list of precession frequencies, reporting on the magnetic environment of a specific hydrogen. This will change if a protein changes its conformation or is bound by another molecule.
Thus NMR is a uniquely sensitive way to study both flexible molecular structures and on-going shifts in a conformation (dynamics). The method can detect weak/transient interactions between molecules, since there will be a change in the precession frequency at their binding site with changes in the magnetic environment as the two chemical groups interact. NMR here can detect such dynamics and interactions occurring as quickly and briefly as mere billionths of seconds (nanoseconds).
Analyzing enzyme dynamics and interactions during a key regulatory event in cell biology
The central dogma of molecular biology states that DNA makes RNA, which makes proteins, and proteins carry out the functions of living organisms. Specifically, messenger RNA (mRNA) carries the blueprints for making specific proteins from encoding genes in the cell nucleus for processing by ribosome factories in the cytoplasm.
Such an essential process of life is by necessity highly regulated. For example, there’s a quality control process disassembling mRNAs (via enzymatic degradation, also known as decay) that are truncated or malformed and would thus generate mutant proteins (nonsense-mediated decay). Also, certain mRNAs are degraded as the end results of sequential protein interactions (pathways) in order to maintain cellular homeostasis, to limit production of a particular protein, or so the cell can make more of other proteins to respond to needs in an animal’s development, cell differentiation/proliferation, and stress/immune responses.
Gene expression can thus be controlled at the level of mRNA (transcript) stability—and failures in such regulation may yield cancers and other diseases.
Department scientists use a variety of biophysical methods, including NMR, to guide and detect the results of biochemical and genetic mutagenesis experiments that dissect the penultimate, irreversible step in numerous eukaryotic mRNA decay pathways. In that step, the mRNA decapping enzyme 2 (Dcp2) removes a structural cap (7-methylguanosine or m7G) via hydrolysis at one end (five prime terminal or 5′ end) of an mRNA, exposing a 5′-monophosphate that is recognized by 5′-to-3′ exonucleases—enzymes that cleave the mRNA’s nucleotides apart starting from that end.
Using yeast as model organisms (key protein domains are conserved in humans) researchers here are discovering the details of how this mRNA decapping is carried out. In particular, they explore how the chemical reaction rate (enzyme kinetics) of this key step in mRNA decay is affected and controlled by rapid changes in the shape of Dcp2 (conformational dynamics) that bring two domains together to form the enzyme’s active site and the weak, very fast, yet critical interactions between Dcp2 and both transcript nucleotides and co-activator proteins in a transient enzyme-substrate complex.
Model of decapping catalysis by Dcp2, which proposes that the above conformational change is used as a point of control by decapping activators.
(a) Dcp2 exists in a conformational equilibrium between open and closed forms.
(b) RNA (with m7G magenta-hexagonal cap) binds to the open form.
(c) After binding the enzyme closes over the RNA substrate, a step that may be enhanced by co-activators.
(d) Following closure, the RNA cap is removed by hydrolysis.
(e) The RNA is then released and subject to further degradation (exonucleolysis) by 5'-3' nucleases.
The function of proteins:
Proteins have many different and varied biological functions and, in addition to their size, shape, and orientation, can be classified according to their biological roles within the cell.
Enzymes catalyze almost every chemical reaction between organic biomolecules in living cells. Enzymes are the most varied and specialized proteins, and many thousands of different types, each capable of catalyzing a distinguished type of chemical reaction, have been revealed in different organisms.
Nutrient and Storage Proteins
Many plants store nutrient proteins inside their seeds. Such proteins are important for the growth and survival of the germinating seedlings. Particularly well-known examples are the proteins found in corn, wheat, and rice seed. Another examples of nutrient proteins are ovalbumin, the significant component protein of egg white and casein, found in milk. Ferritin is found in some bacteria and also in plant and animal tissues which stores iron.
Some proteins give cells and organisms with the ability to contract, change conformation, and are known as contractile or motile proteins.
Actin and myosin play a role in the contractile system of skeletal muscle and are also found in many non-muscle cells. Microtubules are formed from the tubulin protein and act in conjunction with the protein dynein in the flagella and cilia of bacteria, which propel the organisms and allow in motility.
Transport proteins allow substances to be carried to their destination. In blood plasma, transport proteins connect and transport specific molecules or ions from one organ to another. Haemoglobin in erythrocytes binds oxygen as blood passes through the lungs, transporting it to the peripheral tissues, and releases it to contribute to the energy-yielding oxidation of nutrients. Blood plasma contains lipoproteins, which carry lipids from the liver to the other organs. Another types of transport proteins are present in the plasma membranes and intracellular membranes of all organisms these are adapted to bind glucose, amino acids, and other substances and transport them across the membrane to the point at which they are utilized.
Many proteins function as supporting filaments, cables, or sheets to give biological structures strength or protection. The main constituent of tendons and cartilage is collagen, a fibrous protein with a very high tensile strength.
An example of this is leather, which comprises almost pure collagen. Ligaments consist of elastin, which is a structural protein that can be stretched in two dimensions. Hair, fingernails, feathers, and horn all contain significant keratin, which is a tough, insoluble protein. The main component of silk fibres and spider webs is fibroin, and the wing hinges of some insects contain resilience. Resilin has ideal elastic properties.
Some proteins also regulate the cellular or physiological activity. Among those proteins are many hormones. Insulin, which regulates in sugar metabolism, and the growth hormone secreted by the pituitary gland, are two examples of regulatory proteins. The cellular response to many hormonal signals is often mediated by a class of GTP-binding proteins, known as G proteins. GTP is closely associated with ATP, where guanine replaces the adenine section molecule. Other regulatory proteins attach to DNA and control the biosynthesis of enzymes and RNA molecules concerned in cell division in prokaryotes and eukaryotes.
Many proteins defend organisms against invasion by another species or protect them from injury. The immunoglobulins or antibodies, which are specialized proteins produced by the vertebrates’ lymphocytes, can recognize, precipitate or neutralize invading microorganisms, and foreign proteins from another species. Fibrinogen and thrombin are blood clotting proteins that stop blood loss when damage occurs in the vascular system. Some snake venom, bacterial toxins, and toxic plant proteins, such as ricin, also appear to have defensive functions. Some of these, including fibrinogen, thrombin, and some types of venom, are also enzymes.
There are numerous other proteins whose functions are exotic and, therefore, are not easily classified. Monellin, a protein from an African plant, has an intensely sweet taste and has been studied for human use as a food sweetener.
Some Antarctic fish possess antifreeze proteins within their blood plasma, which prevents their blood from freezing.
Protein and it&rsquos Structure &ndash Explained!
John J. Berzelius (1838) first coined the term ‘protein’ (Gr. proteios — of the first rank) to stress the importance of this class of polymers.
Proteins are the macromolecules composed of one or more polypeptide chains, each of which is a mixed polymer of L-a-amino acid residues joined end-to-end by peptide bonds.
Monomeric protein consists of single polypeptide chain, e.g., lysozyme, myoglobin. The oligomeri c or multimeric protein consists of 2 or more polypeptide chains, each of which is called a protomere or subunit. Rubisco consists of 24 polypeptides, hemoglobin (Hb) is a tetrameric consists of two a-chains and two β- chains, immunoglobulins consists of 2 H-chains and 2H-chains etc.
Structure of Proteins:
A polypeptide chain is synthesized on the ribosome as a linear sequence of amino acids. Just after the synthesis, the newly synthesized (nascent) polypeptide folds into a specific three dimensional shape called conformation. The conformation adopted by polypeptide to perform the biological activity is called native conformation.
Previously, it was thought that proteins fold spontaneously to attain their native states. Recent studies revealed that chaperone proteins accelerate the folding process of nescent polypeptides into their native conformations. The deficiencies of chaperone proteins cause diseases due to incorrect folding of proteins. For example, in Alzheimer disease the amyloid plaques develop due to protein clumping in brain cells.
Levels of Protein Structure:
The structure of protein can be described in terms of four levels of organizations: Primary, Secondary, Tertiary and Quaternary. Recent studies revealed two additional levels of protein organization i.e. Super- secondary structures or motifs and domains.
A. Primary (1°) Structure:
Primary structure of a protein means the sequences amino acid residues of its polypeptide chain (s) which read in N-terminus → C-terminus direction. It is the 1st level of organization of protein determined by the codons of mRNA or cistron of DNA. The 1° structure is stabilized by the peptide bonds as well as and disulfide bonds between cysteine residues, if there are any.
Frederick Sanger (1953) first determined the 1° structure of bovine insulin. Now, the 1° structure of a polypeptide is determined by an automated device called spinning cup sequenator, developed by Pehr Edman and Geoffrey Begg.
B. Secondary (2°) structure:
Protein 2° structure refers to the spatial arrangement of backbone atoms of polypeptides without considering the conformations of side chains. The common types of secondary structures are α-helix and β-pleated sheet. The type of 2° structure of a polypeptide depends upon its amino acid composition. The α-helix formation is favoured by alanine, leucine, glutamate and methionine residues, whereas β- sheet is favoured by valine, isoleucine and tyrosine residues.
The backbone atoms of a polypeptide chain tightly coiled in a right-handed manner to form many rod-like structures at intervals called a-helices. For example, the single polypeptide chain of myoglobin contains 8 helices. On the outside of helix the side chains extend outward in a helical manner.
The length of each helix usually varies from 1.7-4.0 nm. In a α-helix, 3.6 amino acid residues present per turn covering a distance (pitch) of 0.54 nm (5.4A). The a-helix is stabilized by hydrogen bonds between the CO group of one amino acid with the NH group of fourth amino acid away. Glycine and proline are often called helix breakers because of their inability to form hydrogen bonds.
About 2-15 polypeptide chains come together to form a β-pleated sheet. The β-pleated sheet is stabilized by hydrogen bonds between CO- and NH groups in different polypeptide chains β- pleated sheet is of 2 types –
Parallel β-sheet – Adjacent chains run in the same direction e.g. β-keratin.
Antiparallel β-sheet – Adjacent chains own in opposite direction e.g. silk fibroin.
Super Secondary Structures:
Two or more secondary structures often aggregate to form a complex structural unit called super secondary structure or motif. Some common motifs are as follows:
C. Tertiary (3°) Structures:
Protein tertiary structure refers to the 3-D structure of an entire polypeptide showing the folding of secondary and super secondary structures to form a compact globular structure. In case of a large polypeptide, that consists of more than – 200 residues form two or more globular units called domains. (A domain is a compact, globular, structurally independent unit that connects with other such unit by peptide backbone). The 3° structure is stabilized by hydrogen bonds, ionic bonds, hydrophobic interactions, Vander Walls force, and London dispersion forces and disulfide bonds if present.
D. Quaternary (4°) Structure:
It is the fourth level of structural organization exhibited only in oligomeric proteins. A protein’s quaternary structure refers to the spatial arrangement of its polypeptide subunits or protomers. In a 4° structure the subunits may or may not be identical, and stabilized by non covalent bonds, e.g., Haemoglobin.
Any partial unfolding or change in 3-D shape that brings a native state of a protein into random coil is called denaturation. But, the separation of subunits in a 4° structure is called dissociation. Proteins are denatured by variety of conditions such as high temperature, variation in pH and ionic concentrations addition of detergents etc. When the normal condition is established smaller denatured proteins refold spontaneously into its native conformation. This is called renaturation but larger protein can rarely renaturate (fold spontaneously) to its native state.
The precise shape of a protein or other macromolecule in three dimensions resulting from the spatial location of the atoms in the molecule. A small change in the conformations of some proteins affects their activity considerably.
Full glossary .
The three-dimensional arrangement of side groups on a molecule which canfreely rotate into different positions without breaking any bonds.
Retrieved from "" .
A conformation of a five-membered ring, e.g. a furanose, in which four ring atoms lie in a plane and C-2 or C-3 (2-endo or 3-endo) is out of the plane. (see also twist conformation)
Return to Search Page .
s are listed below in order of electrophoretic mobility (speed for a given applied voltage) from slowest to fastest: .
An alteration in shape that is a result of binding a substrate molecule.
al changes in a protein often lead to changes in the protein's affinity toward a particular substrate. This process can play a crucial role in regulating the intracellular localization of a protein.
ally and linear binding sites on the glycoprotein B molecule have been mapped by Bioinformatic analysis. Linear binding sites have two conservative linear epitopes on SU segment and also two linear antibody sites on TM segment (Britt, Jarvis, Drummond, & Mach, 2005).
al Change - A structural shift in an enzyme due to the formation of the enzyme substrate complex.
Intermediate - A molecule that serves no function, but exists as a part of a pathway to another molecule.
During this hydrogenation process, double bonds of the cis-
in the hydrocarbon chain may be converted to double bonds in the trans-conformation. This forms a trans-fat from a cis-fat. The orientation of the double bonds affects the chemical properties of the fat.
"Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded
s and show directional differences in stacking pattern" (PDF). Biochemistry. 43 (51): 15996-6010. doi:10.1021/bi048221v. PMID 15609994. Archived (PDF) from the original on 10 June 2007.
a model of an enzyme-substrate reaction that causes a
al change in the active site of the enzyme that allows the substrate to fit perfectly
Induced pluripotent stem cells
somatic (adult) cells reprogrammed to enter an embryonic stem cell-like state
The sequential model of allostery holds that subunits are not connected in such a way that a
Autodock VINA docking software was used to investigate how the ligand binds to the respective protein, the binding
, functionally interacting residues and best structural information. The ligand retrieved for DAOA is described in Table2 and its structure is illustrated in Figure5 (a and b).
[Normally], when a hormone binds to a receptor, you get these really neat
al changes that then cause gene expression to ensue. Most androgen insensitivity cases involve mutations where the hormone would be binding.
Smo protein accumulates specifically in cells in which Ptc activity is absent or abrogated by Hh signaling, a process that seems to involve the redistribution of a hyperphosphorylated form of the protein to the cell surface (Denef, 2000) and may also be accompanied by a
Carrier proteins allow specific molecules to cross the cell membrane by undergoing a
al change opens a hole through which the molecule can enter or exit a cell.
Conditions that alter the
of a protein which regulates expression of other genes.
When it binds to the allosteric site it acts as non-competitive inhibitor and changes the
of the active site. Therefore, it makes the binding of the substrate to the enzyme unlikely.
The tertiary structure of a protein is a spatial
in addition to the secondary structure, in which the alpha-helix or the beta-sheet folds itself up.
al change of the receptor causes the G protein complex (pink, right) to become activated and uncoupled. The G protein stimulates adenylate cyclase (red, left) to convert ATP (the cell&aposs energy molecule) into cAMP (a signaling molecule, blue).
Polymorphism. A gel-based means for detecting single nucleotide changes within allelic PCR products that have been denatured and gel-fractionated as single strands.
SSLP Simple Sequence Length Polymorphism see microsatellite.
SSR Simple Sequence Repeat see microsatellite.
D. the allosteric enzyme is locked in an inactive
E. all substrate has been converted to product
The Biology Project
Department of Biochemistry and Molecular Biophysics
University of Arizona
Wednesday, September 25, 1996
Contact the Development Team .
For proteins, a process in which a protein unravels and loses its native
, thereby becoming biologically inactive. For DNA, the separation of the two strands of the double helix. Denaturation occurs under extreme conditions of pH, salt concentration, and temperature.
Another protein family related to muscular contraction is the troponin family, regulating the binding of myosin to actin via
differences dependent on the calcium ion concentration in the cells.
5) The tertiary structure of a protein is the 3 dimensional
that the peptide folds into due to the collective forces of hydrophobic interactions, hydrogen bonds, salt bridges and disulfide bonds.
carrier proteins - membrane transport protein that binds to a solute and transports it across the membrane by undergoing a series of
Channel proteins - form hydrophilic pores that extend across the lipid bilayer when these pores open, they allow specific molecules to pass through them .
Chaotropic agents such as thiocyanate (SCN-), chlorate (ClO3-), or guanidinium, disrupt the structure of water and thereby promote the solubility of nonpolar substances and promote changes in protein
that for example may affect migration through a chromatographic medium.
RNA binding protein. A protein whose
and play of forces is such that it can bind to RNA molecules based on particular sequences or structures or other features of the RNA.
A substance that reduces the activity of an enzyme by binding to a location remote from the active site, changing its
so that it no longer binds to the substrate.
noncyclic electron flow .
Allosteric Site: A non-active site on the enzyme body, where a non-substrate compound binds. This may result in
al changes at the active site.
Allotype: Any of various allelic variants of a protein, characterized by antigenic differences.
Motifs have been determined in HPr that are crucial, and highly specific, to the molecular interactions of HPr with its targeted Enzyme IIA domains [J Bacteriol]. Because binding between EI and HPr does not involve significant
al changes HPr acts as a phospho-relay between EI and the Enzyme II complexes [J .
The motor proteins involved in organelle transport operate by altering their three-dimensional
using adenosine triphosphate (ATP) as fuel to move back and forth along a microtubule.
A molecule that binds to a receptor is called a ligand, and may be a peptide (such as a neurotransmitter), a hormone, a pharmaceutical drug or a toxin, and when such binding occurs, the receptor goes into a
Welcome to the CBM!
At the Center for BioMolecular Modeling, teachers come first.
We work closely with talented science educators from across the US to create innovative instructional materials that make the biosciences understandable.
Our flagship outreach program in which students design and 3D print a physical protein model.
Protein Modeling Competition
A national competition in which students compete to build the best protein model.
Our undergraduate modeling program in which students study and model cutting edge research.
Professional Development Courses
Visit the CBM to learn how to confidently use physical models in your classroom.
Meet us at regional and national educational conferences throughout the year.
Borrow from our free extensive collection of educational modeling activities for use in your own classroom.
A wide collection of digital tools, activities and training resources to complement our physical models.
Our most popular modeling kits are available for purchase.
What's New From the CBM?
A New Antibody MAPS Module
This new MAPS Module will focus on antibodies and their role in our immune system. With everyone’s current focus on a coronavirus vaccine, we thought this would be a timely topic. There are many fascinating stories of current research involving antibodies that your students can explore.
An obvious choice would be the structure of an antibody binding to a coronavirus protein. We will highlight one fascinating story involving a synthetic biology approach to create a nanobody (single-domain antibody) that locks down the coronavirus spike protein into an inactive conformation.
This paper describes our work over the past twenty years. Check it out, and see how you relate to various aspects of our program!
Check out the Molecule Maker!
Many schools now have access to low cost 3D printers, but finding 3D print files (.STL) of specific small molecules can be challenging.
With the CBM's new Molecule Maker, students and teachers can draw chemical structures and export their molecule as an .STL file for 3D printing. The left side of the screen is an interactive chemical draw program called JSME Molecular Editor. This chemical draw program communicates with the live Jmol program on the right side of the screen, displaying the molecule in a fully interactive 3-dimensional display.
Any small molecule created with the CBM's Molecule Maker can then be exported as an image (.JPG), a molecular structure file (.MOL) or a 3D print file (.STL) that can be used on any desktop 3D printer. Check it out at https://cbm.msoe.edu/modelingResources/moleculeMaker/
A New CBM Publication
The CBM has just published a paper in the Journal of STEM Outreach entitled "A Strategy for Sustained Outreach in the Molecular Biosciences".
This paper describes our work over the past twenty years. Check it out, and see how you relate to various aspects of our program!
What are Physical Models?
The invisible world of molecules becomes real when students hold physical models in their hands. Models function as thinking tools that stimulate questions and are a key component of the Next Generation Science Standards.
The MSOE Center for BioMolecular Modeling uses 3D Printing Technology to create physical models of protein and molecular structures. They are designed using the molecular Visualization software Jmol and then exported as 3D files.
What Teachers and Students are Saying About the CBM
"Models give the students an opportunity to discover on their own, rather than having you tell it to them."
"These curriculum modules tie what seems like a really abstract idea--some little change in a molecule you can’t even see—to their own health. That’s really compelling. This stuff isn’t in any textbook."
"The fact that they were so teacher-focused was refreshing."
"The CBM staff let us be learners, and they respected us."
"Watching the CBM staff, who are masters, and being given these models is wonderful. Now we have powerful knowledge and powerful examples that we can put in our kids’ heads. I’m so excited for the school year to start, I don’t want to have to wait two months!"
"It was an amazing workshop. Foundational pieces of biology are woven through these stories."
"It really opened up science to me as a student. Science isn't sitting in a classroom learning about rocks its about being in a lab doing research alongside your mentor."
The [MAPS] Team program has taught me the importance of actively participating in the scientific community, being professional, and having the ability to take something complex and put it into simpler yet accurate terms."
"This program has opened my eyes to an entirely new career field. I have learned so much through this experience and I am extremely grateful that I have experienced this."
Most proteins contain one or more stretches of amino acids that take on a characteristic structure in 3-D space. The most common of these are the alpha helix and the beta conformation.
The R groups of the amino acids all extend to the outside.
- The helix makes a complete turn every 3.6 amino acids.
- The helix is right-handed it twists in a clockwise direction.
- The carbonyl group (-C=O) of each peptide bond extends parallel to the axis of the helix and points directly at the -N-H group of the peptide bond 4 amino acids below it in the helix. A hydrogen bond forms between them [-N-H·····O=C-]
- consists of pairs of chains lying side-by-side and
- stabilized by hydrogen bonds between the carbonyl oxygen atom on one chain and the -NH group on the adjacent chain.
- The chains are often "anti-parallel" the N-terminal to C-terminal direction of one being the reverse of the other.
ICM—A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation
An efficient methodology, further referred to as ICM, for versatile modeling operations and global energy optimization on arbitrarily fixed multimolecular systems is described. It is aimed at protein structure prediction, homology modeling, molecular docking, nuclear magnetic resonance (NMR) structure determination, and protein design. The method uses and further develops a previously introduced approach to model biomolecular structures in which bond lengths, bond angles, and torsion angles are considered as independent variables, any subset of them being fixed. Here we simplify and generalize the basic description of the system, introduce the variable dihedral phase angle, and allow arbitrary connections of the molecules and conventional definition of the torsion angles. Algorithms for calculation of energy derivatives with respect to internal variables in the topological tree of the system and for rapid evaluation of accessible surface are presented. Multidimensional variable restraints are proposed to represent the statistical information about the torsion angle distributions in proteins. To incorporate complex energy terms as solvation energy and electrostatics into a structure prediction procedure, a “double-energy” Monte Carlo minimization procedure in which these terms are omitted during the minimization stage of the random step and included for the comparison with the previous conformation in a Markov chain is proposed and justified. The ICM method is applied successfully to a molecular docking problem. The procedure finds the correct parallel arrangement of two rigid helixes from a leucine zipper domain as the lowest-energy conformation (0.5 Å root mean square, rms, deviation from the native structure) starting from completely random configuration. Structures with antiparallel helixes or helixes staggered by one helix turn had energies higher by about 7 or 9 kcal/mol, respectively. Soft docking was also attempted. A docking procedure allowing side-chain flexibility also converged to the parallel configuration starting from the helixes optimized individually. To justdy an internal coordinate approach to the structure prediction as opposed to a Cartesian one, energy hypersurfaces around the native structure of the squash seeds trypsin inhibitor were studied. Torsion angle minimization from the optimal conformation randomly distorted up to the rms deviation of 2.2 Å or angular rms deviation of l0° restored the native conformation in most cases. In contrast, Cartesian coordinate minimization did not reach the minimum from deviations as small as 0.3 Å or 2°. We conclude that the most promising detailed approach to the protein-folding problem would consist of some coarse global sampling strategy combined with the local energy minimization in the torsion coordinate space. © 1994 by John Wiley & Sons, Inc.