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Phys 4500: Computational Biological Physics Winter 2005

Basics of (Bio)Molecular Modeling


•Biopolymers: structure, function
•Amino acids and proteins
•Molecular visualization with VMD
•PDB files
•Proteins: conformation, dynamics
•Computer simulation methods: MD, MC, QC

Hands-On

•Download protein structures from the Protein Data Bank


•VMD tutorial 1 (Basics)
•Tcl scripting (TclTutor)
•VMD tutorial 2 (Multiple molecules and scripting)

Protein Conformation (3D structure)


- described by the spatial coordinates (x,y,z) of all
constituent atoms (nuclei)

` Born-Oppenheimer approximation
nuclear mass >> electronic mass
⇒ electronic motion can be decoupled from the
nuclear motion
` atomic model of proteins: nuclei of constituent
atoms (charged point particles) connected
through chemical bonds (determined by
overlapping electronic clouds)

Ψ (r, R ) ≈ ψ (r | R ) Θ(R ) 01
electronic nuclear wave function
Protein Dynamics
` electronic motion is governed by Quantum
Mechanics (QM)
→ QM simulations (Quantum Chemistry
calculations)
→ numerical solution of the Schrödinger
equation
→ Potential Energy Surface (PES): U(R)
` nuclear motion is semi-classical and can be
described by classical mechanics
→ Molecular Dynamics (MD) simulations
→ integrate Newton’s eqs. of motion

mj d 2 R j /dt 2 = −∇ j U( R )

Computer Simulation Methods


` Quantum Mechanics/Chemistry (QM/QC)
• PES, charge density
• ab initio, semi empirical, density functional
` Molecular Dynamics (MD)
• samples phase space (r,p)
• equilibrium vs non-equilibrium MD
• Newtonian, Langevin, Brownian, etc. MD
• MD in NVE, NVT and NPT ensembles
` Monte Carlo (MC)
• samples configuration space
• classical MC (Metropolis MC, biased MC)
• quantum MC (VMC, GFMC, DMC, PIMC)
` Combined QM/MD
• PES calculated on the fly

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Protein Structures are determined
by X-ray crystallography
electron density map

atomic nuclei
are located at
high electron
densities
final, refined structure

PDB files
` PDB files (downloaded from the Protein Data Bank)
contain standard records for species, tissue,
authorship, citations, sequence, secondary structure,
etc.
` We only care about the ATOM records…
` atom name (N, C, CA)
` residue name (ALA, HIS)
` residue id (integer)
` coordinates (x, y, z)
` occupancy (0.0 to 1.0)
` temperature (B-) factor
` segment id (6PTI)
` PDB files from the Protein Data Bank contain NO
hydrogen atoms! (need to be added when building the
system)
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PDB file format
======================= ATOM ===============================
COLUMNS DATA TYPE FIELD DEFINITION
-------------------------------------------------------------
1 - 6 Record name "ATOM "
7 - 11 Integer serial Atom serial number.
13 - 16 Atom name Atom name.
17 Character altLoc Alternate location indicator.
18 - 20 Residue name resName Residue name.
22 Character chainID Chain identifier.
23 - 26 Integer resSeq Residue sequence number.
27 AChar iCode Code for insertion of residues.
31 - 38 Real(8.3) x Orthogonal coordinates for X in
Angstroms.
39 - 46 Real(8.3) y Orthogonal coordinates for Y in
Angstroms.
47 - 54 Real(8.3) z Orthogonal coordinates for Z in
Angstroms.
55 - 60 Real(6.2) occupancy Occupancy.
61 - 66 Real(6.2) tempFactor Temperature factor.
73 - 76 LString(4) segID Segment identifier, L-justified.
77 - 78 LString(2) element Element symbol, right-justified.
79 - 80 LString(2) charge Charge on the atom.

ATOM 1 N MET 1 27.340 24.430 2.614 1.00 9.67 1UBQ 71


ATOM 2 CA MET 1 26.266 25.413 2.842 1.00 10.38 1UBQ 72
ATOM 3 C MET 1 26.913 26.639 3.531 1.00 9.62 1UBQ 73
ATOM 4 O MET 1 27.886 26.463 4.263 1.00 9.62 1UBQ 74

Protein Structure File (PSF)


atomic properties (mass, charge, type)
` Every atom in the system is listed.
` Provides all static atom-specific values:
` atom name (N, C, CA)
` atom type (NH1, C, CT1)
` residue name (ALA, HIS)
` residue id (integer)
` segment id (6PTI)
` atomic mass (in atomic mass units)
` partial charge (in electronic charge units)
` What is not in the PSF file?
` coordinates (dynamic data, initially read from PDB file)
` velocities (dynamic data, initially from Boltzmann
distribution)
` force field parameters (non-specific, used for many
molecules)
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Hands-on: VMD Tutorial (2)

Hands-on: Tcl scripting


TclTutor will teach you the basics (and much more) of
the Tcl scripting language. First learn just what is
needed for using the recuired VMD features!

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