Two types of MC moves are performed:

1. Simple moves for torsion angles of amino acid side chains in the loop; and
2. Local moves for the seven consecutive backbone torsion angles in a window of loops.

To reduce the computational cost of energy evaluation in this method we developed a potential map, which include van der Waals, electrostatics, hydrophobic as well as hydrogen bond potentials to replace the bulk protein environment and solvation effect.

We reparametrized the distance-dependent dielectric function of Mehler and Solmayer to work in conjunction with the desolvation and hydrogen-bonding terms used.

To improve the efficiency of LMMC sampling we employed a two-step protocol:

1. Loop sampling at high temperature by using a reduced potential map to lower the energy barriers for exploring a larger conformational space;
2. Clustering of loop conformations extracted from the high-temperature run followed by multiple simulated annealing simulations to identify the loop conformations in local energy minima.

Local Move Monte Carlo Sampling: LMMC loop sampling starts with changing one backbone torsion angle followed by the adjustment of the six subsequent torsions to allow the rest of the loop to remain in its original position while preserving all bond lengths and bond angles.

Loop structures of PDB ID 5cpa (231-237) produced by local move MC method at 5000K and followed by clustering to generate 100 representative conformations. Black stick represents the crystal loop structure, and gray wires represent the 100 representative loop conformations.

Potential energy

Interactions with the rigid part is represented over grids, based on Autodock types

Comparison with other methods

. Comparison of loop prediction results from local move MC (LMMC) simulated annealing method and others (The results are based on the backbone global RMSD (in Å) between the crystal and predicted loop structures).

*: Crystal packing information is included for loop prediction by LMMC method only. (a). Results from our Local Move Monte Carlo approach; (b). Results from our Local Move Monte Carlo approach followed by energy Minimization; (c). Data taken from Table 8 of Vlijmen and Karplus; (d). Data taken from Table 9 of Deane and Blundell; (e). Data taken from Table VI of Deane and Blundell; (f). Data taken from Table 2 of Fiser et al.; (g). Data taken from Table II of Michalsky et al.; (h). Data taken from Table I of Rohl et al.

Last modified: 11/29/02 (MM)