Method and expert system of molecular mechanics force fields for computer simulation of molecular systems

#The invention relates to the field of Computer Aided Molecular Design (CAMD) and, in particular, to systems and methods those simulate molecular behavior and predict the chemical and physical properties of molecules using computers (Molecular Modeling). Specifically, the invention relates to an expert system that automatically generates molecular mechanics force field parameters for computer simulation of molecular systems.

#A molecular mechanics force field is a set of mathematical functions containing adjustable parameters. By adjusting the parameters, a molecular mechanics force field can be made to accurately describe inter-atomic interaction energies as functions of the atomic coordinates for a molecular system. Because all physical properties of a molecular system are determined by the interaction energies, a molecular mechanics force field is a fundamental component in molecular modeling.

#Several general molecular mechanics force fields have been developed (e.g., CHARMM, AMBER, MM2, MM3, MMFF, CFF, COMPASS)[1-7]. These force fields perform well for molecular systems that have been explicitly parameterized, but not well for many others that have not been so parameterized because the required parameters are substituted by transferring parameters from similar molecules. Due to the massive number of possible chemical structures that can be made, it is impractical to have one force field that provides a complete coverage for all applications. Frequently, incomplete force field coverage is the stumbling block in “real-life” molecular modeling in various fields such as pharmaceutics, chemicals, and materials.

#A more complete appreciation of the present invention and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein:

#FIG. 1 is a top-level system block diagram and data flows for performing calculations, according to the present invention;

#FIG. 2a is block diagram of data flows of the COMPUTATION ENGINE 105 component of FIG. 1, according to the present invention;

#In the preferred embodiment of the invention, a computer software program is implemented to enable fast development of molecular mechanics force field parameters.

#A high-level logical architecture of the program is illustrated in FIG. 1. The program consists of a graphical user interface (GUI) 101, a computational engine 105, a database 108, an interface 102 to quantum mechanics ab initio calculation software, and an interface 107 to a molecular mechanics simulation software.

#Various computer languages can be used in implementing the software. For example, the graphic user interface 101 is implemented using JAVA, although any other language (for example, C, C++) may be used. The utilization of JAVA maximizes the platform independence that is, the program can be run without re-compiling the software on different operating systems such as Windows, Macintosh, Linux, Unix machines, etc. The computational engine 105 is implemented using C++ for maximum computational efficiency. The portability is enhanced by restricting language utilization to ANSI standard, enabling the program to be compiled on different platforms without modification of the source code.