From electron and nuclei to atoms to molecules to macromolecules

IBM, Kingston, USA.

Abstract

Biomolecular simulations are a bit like the tip of an iceberg, indeed their base goes very deep. Let us start down at the bottom and move to the top, considering for example the problem of protein folding or other problems in S.A.R. with water, proteins and nucleic acids. There are a number of possible starting points but we shall emphasize a specific one, called "Global Simulation Approach". First with quantum mechanics we assemble atoms starting from nuclei and electrons (Notice that for heavy atoms we need relativistic quantum mechanics). Then from atoms we build molecules again using quantum mechanics. We shall present C60 and nitrogonase as examples. Then we can move to molecular dynamics either classical or quantum (for example with the Carr-Parrinello approach). Examples are

• i)

  C60 cluster once more,

• ii)

  a simulation for 1000 water molecules with a new flexible, polarizable water- water potential (Niesar-Clementi-Corongiu), and

• iii)

  BPTI in solution.

At this stage we would like to extend the scale of simulation time from pico to nanoseconds: this may be accomplished with stochastic dynamics simulations, based on molecular dynamic trajectories. Here we could stop for a moment! But instead let us now try a different path from the top down. We shall use neural networks to guess the structure of BPTI starting from its sequence and use this guess as input for stochastic dynamics. All this and much more will be available for MOTECC-91.