Most biological processes are initiated by the association of ligands and proteins; therefore, it is critical to obtain the detailed knowledge of molecular encounter processes. In this work, we applied Brownian dynamics algorithm with coarse-grained model and atomistic molecular dynamics simulations to investigate kinetic mechanism of molecular recognition. Through studying the case of HIVp and its neutral binders, we showed a series of binding intermediates of two ligands. The slower binder displays complicated conformational transition during association processes. Generally, charge attractions play a key role for ligand to target the specific part of protein, which is also coordinated by arrangements of non-polar interactions. Moreover, we examined water effects and found that water molecules are highly mobile and form connections to mediate protein-ligand interactions. The desolvation process can accelerate the binding processes. Our work brings insights into ligand-protein associations and assists in the design of targeted ligands.

Modeling of ligand and HIV-1 protease association by molecular dynamics study

246th National Meeting (2013)

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