One of the computational “grand challenges” is to develop methodology capable of sampling conformational equilibria in systems with rough energy landscapes. Here, a significant step forward is made by combining molecular dynamics with a novel variable transformation designed to enhance sampling by reducing barriers without introducing bias and, thus, to preserve, perfectly, equilibrium properties.

• Received 28 March 2001

DOI:https://doi.org/10.1103/PhysRevLett.88.100201