Simulation of Multi-Protein systems

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Simulation of large multi-component molecular assemblies with atomistic details is an important step toward understanding cellular processes. The goal of this proposal is to develop an efficient method for the simulation of multi-protein systems consisting of many copies of a few types of proteins, each in a number of discrete conformations. The basis for our approach is the observation that the interaction energy between two proteins (or discrete protein conformations within an ensemble) – can be efficiently calculated over the entire rotational-translational space using the fast Manifold Fourier transform (FMFT) correlation approach. Given any conformation of a complex multi-particle system, its energy can be easily obtained by summing the pairwise interaction energies extracted from the lookup tables. The key innovation to efficiently implement this method is our ability to compress and store the interaction energy lookup tables in memory using wavelet sets. We will apply the method in two application. The first is simulation of multi-protein assemblies and their association pathways, possibly in conjunction with low resolution Mass Spectrometry (MS) and EM data, providing mechanistic insight into cellular function. The second is simulation of protein aggregation and crowding, which is important for the fundamental understanding of cell biology and therapeutic development.