Question

When implementing alchemic mutations in molecular dynamics simulations, a w value, or soft core potential is used. What is a soft core potential? What non-bonded interaction does is perturb?

How are the alchiemic mutations used to calculate solvation free energy of a molecule such as toluene?

Answer 1

• This question is based on molecular dynamics which is also related to thermodynamics.
• Mutation is the process of changing the structure of a gene, which results in a variant form that may be transmitted to subsequent generations which caused the alteration of single base units in DNA, or the deletion, insertion, or rearrangement of larger sections of genes or chromosomes. In other words we can say Mutation is the only way in which new variation enters into the species.
• In modern computational chemistry, the estimation of free energies is an important aspect. Alchemical methods which is based on Molecular Dynamics allows the accurate calculations of free energies. The alchemical methods are also applied in predicting the protein−ligand binding free energies, which has a great importance in rational drug design. Molecular Dynamics based alchemical methods are also used to estimate free energies of solvation of ligands.
• Molecular dynamics based free energy calculations allows the determination of various thermodynamic quantities from computer simulations of varieties of small molecules. Thermodynamic integration calculations can suffer from instabilities during the creation or annihilation of particles. This problem may be addressed with soft-core potential functions. Soft-core potential functions keeps pairwise interaction energies which is finite for all configurations and provides smooth free energy curves. Soft-core potential energy curves drawn between two atoms with a function of distance.