GPU-Accelerated Computation of Solvation Free Energy for Kinetostatic Protein Folding Simulation

2013 ◽  
Author(s):  
Morad Behandish ◽  
Pouya Tavousi ◽  
Horea T. Ilieş ◽  
Kazem Kazerounian
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Graphics Processing Units ◽  
Solvation Free Energy ◽  
Van Der Waals Interactions ◽  
Molecular Surface ◽  
Efficient Computation ◽  
Performance Improvements ◽  
Folding Simulation ◽  
Computational Bottleneck

A realistic computer simulation of protein folding requires a comprehensive account of interaction energetics, placing a substantial demand on processing power. This paper presents an improved computational framework for protein folding software package PROTOFOLD, that enables efficient computation of solvation free energy effects in addition to Coulombic and van der Waals interactions. Efficient data structures have been utilized to speed-up the sequential running times from O(n2) to O(n), n being the number of atoms. It turns out, however, that an accurate evaluation of molecular surface areas characterizing the solvation effects imposes a computational bottleneck to the entire simulation. Massive computational power offered by Graphics Processing Units (GPU) was exploited to develop a simple and efficient Single-Instruction Multiple-Thread (SIMT) algorithm for the latter step. The running times were monitored for different steps of the folding simulation for different molecular sizes. Significant performance improvements were observed, yielding promising results where numerous iterative runs are needed.

An Improved Free Energy Formulation and Implementation for Kinetostatic Protein Folding Simulation

2013 ◽  
Author(s):  
Pouya Tavousi ◽  
Morad Behandish ◽  
Kazem Kazerounian ◽  
Horea T. Ilieş
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Structure Prediction ◽  
De Novo ◽  
Small Time ◽  
Van Der Waals Interactions ◽  
Folding Simulation ◽  
Aqueous Solvent ◽  
Speed Up ◽  
Energy Formulation

Protein structure prediction remains one of the significant challenges in computational biology. We have previously shown that our kinetostatic compliance method can overcome some of the key difficulties faced by other de novo structural prediction methods, such as the very small time steps required by the molecular dynamics approaches, or the very large number of samples required by the sampling based techniques. In this paper we extend the previous free energy formulation by adding the solvent effects, which contribute predominantly to the folding phenomena. We show that the addition of the solvation effects, which complement the existing Coulombic and van der Waals interactions, lead to a physically effective energy function. Furthermore, we achieve significant computational speed-up by employing efficient algorithms and data structures that effectively reduce the time complexity from O(n2) to O(n), n being the number of atoms. Our simulations are consistent with the general behavior observed in protein folding, and show that the hydrophobic atoms tend to pack inside the core of the molecule in an aqueous solvent, while a vacuum environment produces no such effect.

Complexity in Protein Folding: Simulation Meets Experiment

2012 ◽  
Vol 2 (1) ◽  
pp. 4-11
Author(s):  
Amedeo Caflisch ◽  
Peter Hamm
Keyword(s):  
Protein Folding ◽  
Folding Simulation

To the fast calculation of the solvation free energy. Combining expanded ensembles with L2MC

2021 ◽  
Vol 42 (11) ◽  
pp. 787-792
Author(s):  
Alexei Nikitin ◽  
Vladislava Milchevskaya ◽  
Alexander Lyubartsev
Keyword(s):  
Free Energy ◽  
Solvation Free Energy ◽  
Fast Calculation

scholarly journals How proteins open fusion pores: insights from molecular simulations

2020 ◽  
Author(s):  
H. Jelger Risselada ◽  
Helmut Grubmüller
Keyword(s):  
Free Energy ◽  
Fusion Proteins ◽  
Graphics Processing Units ◽  
Fusion Reaction ◽  
Molecular Simulations ◽  
Minimum Free Energy ◽  
Free Energy Calculations ◽  
Coarse Grained ◽  
Fusion Pore ◽  
Graphics Processing

AbstractFusion proteins can play a versatile and involved role during all stages of the fusion reaction. Their roles go far beyond forcing the opposing membranes into close proximity to drive stalk formation and fusion. Molecular simulations have played a central role in providing a molecular understanding of how fusion proteins actively overcome the free energy barriers of the fusion reaction up to the expansion of the fusion pore. Unexpectedly, molecular simulations have revealed a preference of the biological fusion reaction to proceed through asymmetric pathways resulting in the formation of, e.g., a stalk-hole complex, rim-pore, or vertex pore. Force-field based molecular simulations are now able to directly resolve the minimum free-energy path in protein-mediated fusion as well as quantifying the free energies of formed reaction intermediates. Ongoing developments in Graphics Processing Units (GPUs), free energy calculations, and coarse-grained force-fields will soon gain additional insights into the diverse roles of fusion proteins.

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