Weili Cui

Conformational Analysis of Flexible Molecules: Location of the Global Minimum Energy Conformation by the Simulated Annealing Method

Abstract A new computational method for the location of the lowest energy conformation of flexible molecules is reported. The technique, called simulated annealing, is discussed and several applications are described.

Conformation Searching Using Simulated Annealing

Protein folding by direct computer-directed conformation searching is not yet possible (Brunger and Karplus, 1991). Two fundamental problems challenge researchers in this area. The first involves the general issue of energy calculations for large molecules, i.e., parameters, solvents, etc. The second is a more fundamental one called the multiple minimum problem. Since the number of possible minima is an exponential function of the number of degrees of freedom (rotatable angles), an a priori search for the lowest-energy solution to such a problem is impossible for more than about 15 rotatable angles, even with today’s fastest computers. A classic example of this type of problem is known as the “Traveling Salesman Problem” (Kalos and Whitlock, 1986). The problem goes as follows: Try to find the shortest route (i.e., cheapest airfare) for a hypothetical salesman as he/she visits an increasing number of cities.

The calculation and synthesis of a template molecule

Abstract This paper discusses an algorithm to compute the geometric requirements for a template molecule. A Program called DESIGN is used to calculate templates by matching vectors from a database of carbon skeleta. Applications of the approach to an epitope of myoglobin and a fragment around the active site of the enzyme thioredoxin is examined. The synthesis of the template molecule 7 is described.

ANNEAL-RING: a new algorithm for optimization of rings using simulated annealing

The exact calculation of the six dependent dihedrals in rings allows smooth deformation by computer and the application of simulated annealing to the location of the global minimum of rings.