Energy sampling against biomolecular ensembles has been of interest over decades. Given the intricate formula of the internal energies of a biomolecular system, the approach to multi-dimensional integral of the ensemble partition function is by far analytically inaccessible. This facilitates the developments and applications of numerical approximations for molecular ensemble sampling and partition function calculation. We address the sampling problem using a novel methodology termed “Movable Type” (MT). Conceptually it can be understood by analogy with the evolution of printing and, hence, the name movable type.<br/>By separating a molecular energy into pair potentials, the MT method simulates the molecular energies through pair potential samplings and combinations. After this method been raised in 2013, we have kept our development and expanded its application scope. In the current MT algorithm, we have set certain rules to progressively decompose a molecular system into components (as the printing forme) with independent integrals over pairwise distances between the components, until the decomposition reaching the atom level. Energy coupling effect is considered as well with iterative energy correction starting from the atom pairwise distance change to every upper level component until the whole molecule. Different energy functions are also incorporated into the MT program package. In the current study, molecular conformations are parallely generated associated with the conformational energy using the MT method with improved accuracy and efficiency.<br/>The MT algorithm is tested against different validation benchmarks including determining the free energy of ligand binding (drug design), small molecule conformational free energy surfaces and the protein apo-holo conformational free energy difference, with both calculation time and accuracy studied.

Further development of the movable-type energy sampling method and its application in the biomolecular systems

251st National Meeting (2016)

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