Lecture Notes

1. Theory and Practice of Biomolecular Modelling Simulation

Recall the ball and stick model of a 1,2-disubstituted ethane introduced at high-school level these days. Ideas related to hindered rotation around a single bond, the instability of an eclipsed conformation relative to its staggered analogue emerge in a visually telling manner. The balls of course represent atoms and the sticks the chemical bonds between atoms. A clash between two unconnected balls upon rotation around the axis of a stick, is interpreted as steric hindrance to rotation. This simple model provides a powerful tool to appreciate strain and stability associated with molecular conformations. It has been a valuable companion in synthetic and mechanistic organic chemistry and in other areas as well. In such a model, from the standpoint of intermolecular forces, there are no attractions between two unconnected atoms and no repulsions either, not even when the two atoms encounter each other - just that they cannot pass through each other. If this behaviour is to be formulated mathematically, one would say that the potential energy between two non-bonded atoms is zero for all distances greater than the sum of their radii and the energy goes to infinity if the distance is less than the above sum. This in the technical jargon is known as a hard sphere model which in a primitive way describes the interaction between two non-bonded atoms...

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2. MMGBSA: Thermodynamics of Biomolecular Systems

The MMGBSA approach employs molecular mechanics, the generalized Born model and solvent accessibility method to elicit free energies from structural information circumventing the computational complexity of free energy simulations. The MMGBSA approach is parameterized within the additivity approximation [1] wherein the net free energy change is treated as a sum of a comprehensive set of individual energy components, each with a physical basis. The approach, when used with modified solvation parameters viz. m2GB model [2], is expeditious and fairly reliable for studying the energetics of bimolecular systems. Especially important is the application of this approach to determine the binding free energies in biomolecular complexes e.g protein-DNA, protein-drug and DNA-drug complexes

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