Lai-yuen, Susana Karina. Nano-scale Molecular Docking and Assembly Simulator (nanodas) with Haptic Force-torque Rendering and Energy Minimization for Computer- Biography

LAI-YUEN, SUSANA KARINA. Nano-scale Molecular Docking and Assembly Simulator (NanoDAS) with Haptic Force-Torque Rendering and Energy Minimization for ComputerAided Molecular Design (CAMD). (Under the direction of Dr. Yuan-Shin Lee). The objective of this research is to investigate and develop computational and haptic interface techniques to improve the search and design of molecular docking, and to facilitate the assembly of molecular components during molecular design. Nano-scale molecular docking and molecular assembly are vital for the discovery and development of medicines, nano-scale devices, and new materials. Molecular docking and molecular assembly processes consist of finding the feasible pathway, and the correct location and orientation between two molecules so that they can remain attached to each other. As one small molecule (ligand) approaches a larger molecule (receptor), the ligand may need to change its conformation until finding one with the lowest interaction energy. Moreover, for a given receptor molecule, a huge number of ligand molecules need to be searched and tested before a potentially active drug can be identified. Therefore, a fast and efficient method to determine the feasibility of the ligand to dock into the receptor is required. In this paper, a new method called NanoDAS (Nano-scale Docking and Assembly Simulator) is presented to determine the feasibility of a ligand reaching the binding site of a receptor. The developed NanoDAS generates a search tree using a potential field analysis method and a local search with randomization technique to identify feasible ligands for docking into a receptor in molecular docking, and to determine the feasibility of nano-scale assembly in molecular design applications. To improve the design of molecular docking and assembly processes, effective users (i.e., scientists or designers) intervention is necessary. In this paper, a 5-DOF (degrees of freedom) force-torque feedback Haptic device is introduced to provide force-torque feedback to users. Through the force-torque feedback haptic interface, a user is able to feel the forces exerted on the ligand by the receptor, and to determine whether the ligand can actually dock into the receptor by considering its conformational changes and finding a feasible path using the proposed NanoDAS. An energy minimization algorithm has also been proposed to find low-energy molecular conformations in real-time. A Two-phase algorithm is proposed to analyze the probability of a ligand to be docked or assembled into another molecule. The first phase determines the feasibility of a ligand to dock into a targeted binding site of a receptor using an iterative searching procedure. The second phase generates a probability graph to examine all the ligand’s feasible paths to find the most likely docking path. The developed Two-phase algorithm can identify the ligands that, although feasible for the targeted binding site of the receptor, posses higher probability towards other binding site than the targeted one. In this paper, computer implementations and practical examples are presented. The results show that the proposed techniques can significantly increase the searching efficiency in the molecular docking and molecular assembly processes. The developed techniques can be used in Computer-Aided Molecular Design (CAMD) and Computer-Aided Drug Design (CADD) applications.