Wrapping Up Viruses at Multiscale Resolution: Optimizing PACKMOL and SIRAH Execution for Simulating the Zika Virus

Autor(es)

Sonora, Martin ^[1] ; Martinez, Leandro ^{[2, 3]} ; Pantano, Sergio ^[1] ; Machado, Matias R. ^[1]

Afiliação do(s) autor(es)

^[1] Inst Pasteur Montevideo, Biomol Simulat Grp, Montevideo 11400 - Uruguay

^[2] Univ Estadual Campinas, Inst Chem, BR-13083861 Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Ctr Computat Engn & Sci, BR-13083861 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CHEMICAL INFORMATION AND MODELING; v. 61, n. 1, p. 408-422, JAN 25 2021.
• Citações Web of Science: 0

Resumo

Simulating huge biomolecular complexes of million atoms at relevant biological time scales is becoming accessible to the broad scientific community. That proves to be crucial for urgent responses against emergent diseases in real time. Yet, there are still issues to sort regarding the system setup so that molecular dynamics (MD) simulations can be run in a simple and standard way. Here, we introduce an optimized pipeline for building and simulating enveloped virus-like particles (VLP). First, the membrane packing problem is tackled with new features and optimized options in PACKMOL. This allows preparing accurate membrane models of thousands of lipids in the context of a VLP within a few hours using a single CPU. Then, the assembly of the VLP system is done within the multiscale framework of the coarse-grained SIRAH force field. Finally, the equilibration protocol provides a system ready for production MD simulations within a few days on broadly accessible GPU resources. The pipeline is applied to study the Zika virus as a test case for large biomolecular systems. The VLP stabilizes at approximately 0.5 mu s of MD simulation, reproducing correlations greater than 0.90 against experimental density maps from cryo- electron microscopy. Detailed structural analysis of the protein envelope also shows very good agreement in root-mean-square deviations and B-factors with the experimental data. The level of details attained shows for the first time a possible role for anionic phospholipids in stabilizing the envelope. Combining an efficient and reliable setup procedure with an accurate coarse-grained force field provides a valuable pipeline for simulating arbitrary viral systems or subcellular compartments, paving the way toward whole-cell simulations. (AU)

• Processo FAPESP: 10/16947-9 - Estrutura, dinâmica e função em proteínas: simulação computacional e desenvolvimento de algoritmos
• Beneficiário: Leandro Martinez
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08293-7 - CECC - Centro de Engenharia e Ciências Computacionais
• Beneficiário: Munir Salomao Skaf
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/14274-9 - Determinação de estruturas de proteínas usando restrições de distância obtidas de experimentos de ligação cruzada: métodos computacionais e aplicações
• Beneficiário: Leandro Martinez
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/24293-0 - Métodos computacionais de otimização
• Beneficiário: Sandra Augusta Santos
• Modalidade de apoio: Auxílio à Pesquisa - Temático