Molecular Structure Prediction by Global Optimization

The CGU (convex global underestimator) global optimization method is used to predict the minimum energy structures, i.e. folded states, of small protein sequences. Computational results obtained from the CGU method applied to actual protein sequences using a detailed polypeptide model and a differentiable form of the Sun/Thomas/Dill potential energy function are presented. This potential function accounts for steric repulsion, hydrophobic attraction, and φ/ψ pair restrictions imposed by the so called Ramachandran maps. Furthermore, it is easily augmented to accommodate additional known data such as the existence of disulphide bridges and any other a priori distance data. The Ramachandran data is modeled by a continuous penalty term in the potential function, thereby permitting the use of continuous minimization techniques.