Representations of molecular surfaces in spherical harmonics for simulation of protein-protein complexes formation

Author(s)

Samuel Reghim Silva

• Document type: Doctoral Thesis
• Press: São Carlos.
• Institution: Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT)
• Defense date: 2018-11-29

Examining board members

Rinaldo Wander Montalvão; Guilherme Menegon Arantes; Antonio Francisco Pereira de Araujo; Ney Lemke; João Renato Carvalho Muniz

• Advisor: Glaucius Oliva; Rinaldo Wander Montalvão

Abstract

Using computer programs to simulate protein complex formation is an important approach for better comprehension of the interaction mechanisms of such molecules. The parametric representation and the Zernike polynomial method are both compact representations of molecular surfaces based on spherical harmonics, used for visualization and comparison of molecules and for protein-protein docking. They pose, however, limitations regarding surface topology and difficulty in representing arbitrary functions. In this study, the representation capacity of such methods were refined to attain high quality reproductions and applicability to arbitrary topologies. Throughout the analysis of several algorithms, the stages of surface mesh calculation and spherical mapping were identified as highly influential on the quality of the spherical harmonics parametric representation, while high sensibility to changes in the function values were identified as an influential factor for projections in 3D Zernike. A surface calculation method that generates a highly regular mesh was adopted and paired with a modern spherical mapping algorithm to yield reconstructions with low level of distortions and high quality surfaces. Similarity among surfaces from different structures in a conformational ensemble were detected to allow sharing of portions of the description among several surfaces, with corresponding reduction in data volume and processing demand and controllable influence of distortions. A new input data organization method improved the reconstruction quality of general functions in 3D Zernike, although introducing a map to restore the function. Results indicate promising application of the methods in highly detailed protein-protein docking. (AU)

• FAPESP's process: 13/20929-4 - Determination of protein-protein complexes from sparse experimental data
• Grantee: Samuel Reghim Silva
• Support Opportunities: Scholarships in Brazil - Doctorate