Modeling Biomolecules: Larger Scales, Longer Durations

The fast growth of molecular modeling as a research tool in biology and medicine has been tightly coupled to the advent of the supercomputer and advances in applied and computational mathematics over the past decade. Three features characterize the progress made to date: bigger molecular systems described in atomic detail, longer simulation time scales, and more realistic representations of interatomic forces. With these improvements, molecular modeling by computer has given us many insights into the relationship between structure and function of biopolymers and drugs. Researchers now find it indispensable for structure refinement.

Still the state of the art in molecular modeling leaves much room for more progress:

  • Simulations of biopolymers must be extended from the current few thousand atoms to systems of 100,000 or more atoms.
  • The time scale of simulations in molecular dynamics must reach beyond the present nanosecond horizon to describe longer processes of biologically relevant duration. Examples are substrate binding, enzyme reactions, and the folding of proteins into their native form.
  • Descriptions of interatomic forces must be improved to include such factors as atomic polarizabilities and to combine molecular modeling and quantum chemical calculations.
  • Molecular dynamics simulations must speed up by several orders of magnitude to allow the increases in system size and time scale that researchers need. To achieve this speed and improve the quality of force-field representations, scientists will exploit advances in processor speed and in numerical and parallel algorithms. The increasingly important role of molecular modeling in biology and chemistry has already led to the formation of multidisciplinary teams to provide the needed knowledge of hardware, software, mathematics and science.

    Our groups are actively developing computer programs with improved schemes for numerical integration, parallelization and efficient and scalable evaluation of electrostatic force fields. These programs are targeted for a variety of scalable shared-memory and distributed-memory machines, including networks of workstations. Describing this current research and its background will give readers a taste of the challenges ahead in computational biology.

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