BIOMOLECULAR STRUCTURE AND MODELING:
Historical Perspective, Introduction to Molecular Modeling, Roots of Molecular modeling in Molecular mechanics. Introduction to X-Ray crystallography and NMR spectroscopy. Introduction to PDB and 3D Structure data, Structure of PDB and other 3D Structure record. Protein Structure Hierarchy: Structure Hierarchy. Helices – Classic αHelix and π Helices, Left-Handed α-Helix and Collagen Helix. β-Sheets - Turns and Loops. Supersecondary and Tertiary structure. Complex 3D Networks. Classes in Protein Architecture – Folds, α-Class, Bundles,Folded leaves, Hairpin arrays. β-Class folds, Anti-parallel β domains, parallel and Antiparallel Combinations. α/β and α+β-Class, α/β Barrels, Open twisted α/β folds, Leucine-rich α/β folds.α+β folds. Quaternary structure. Discussions with case studies.
FORCE FIELDS:
Formulation of the Model and Energy, Quantifying Characteristic Motions, Complex Biomolecular Spectra, Spectra as force constant sources, In-Plane and Out-of-Plane Bending. Bond Length Potentials - Harmonic term, Morse term, Cubic and Quadratic terms. Bond Angle Potentials - Harmonic and Trigonometric terms, Cross bond stretch / Angle bend terms. Torsional potentials - Origin of rotational barriers, Fourier terms, Torsional parameter Assignment, Improper torsion, Cross dihedral/Bond angle, Dihedral terms. Van der Waals potentials. Rapidly decaying potential. Parameter fitting from experiment. Two parameter calculation protocols. Coulomb potential - Coulomb’s Law. Slowly decaying potential, Dielectric function and Partial charges. Discussions with case studies
MOLECULAR MODELING:
Modeling basics. Generation of 3D Coordinates Crystal data, Fragment libraries, and conversion of 2D Structural data into 3D form. Force fields, and Geometry optimization. Energy minimizing procedures - Use of Charges, Solvent effects and Quantum Mechanical methods. Computational tools for Molecular modeling. Methods of Conformational analysis - Systematic search procedures, Monte Carlo and molecular dynamics methods. Determining features of proteins - Interaction potential, Molecular electrostatic potential, molecular interaction fields, Properties on molecular surface and Pharmacophore identification
3D QSAR METHODS:
Comparative protein modeling – Conformational properties of protein structure, Types of secondary structural elements, Homologous proteins. Procedures for sequence Alignments, Determination and generation of structurally conserved regions, Construction ofstructurally variable regions, SideChain modeling, Secondary structure prediction, Threading methods. Optimization and Validation of Protein Models with suitable case studies. Computation of the Free Energy: Free energy calculations in Biological Systems - Drug design, Signal transduction, Peptide folding, Membrane protein association, Numerical methods for calculating the potential of mean force, Replica-Exchange-Based Free-Energy Methods
MEMBRANE PROTEIN SIMULATIONS:
Membrane proteins and their importance, Membrane protein environments in vivo and in vitro. Modeling a complex environment - Simulation methods for membranes, Membrane protein systems, Complex solvents, Detergent micelles, Lipid bilayers, SelfAssembly and Complex systems. Modeling and Simulation of Allosteric regulation in enzymes - Discussions with case studies. Electrostatics and Enhanced Solvation Models: Implicit solvent electrostatics in Biomolecular Simulation, New distributed multipole methods. Quantum mechanical principles and applications to force field development with case studies