---
abstract: 'Techniques for simulating molecules whose conformations satisfy constraints are presented. A method for selecting appropriate moves in Monte Carlo simulations is given. The resulting moves not only obey the constraints but also maintain detailed balance so that correct equilibrium averages are computed. In addition, techniques for optimizing the evaluation of implicit solvent terms are given.'
author:
- '[Charles F. F. Karney](http://charles.karney.info)'
- 'Charles F. F. Karney'
- 'Jason E. Ferrara'
bibliography:
- 'free.bib'
nocite:
- '[@qiu97]'
- '[@hawkins95]'
- '[@hawkins96]'
- '[@tsui00]'
- '[@tsui01]'
- '[@onufriev04]'
- '[@go70]'
- '[@dodd93]'
---

=2005=8=17

Introduction
============

When attempting to compute thermodynamic quantities with a molecular simulation, we are frequently confronted with the problem of sampling in a high-dimensional configuration space. The dimensionality of this space is given by the number of degrees of freedom for the molecular system. Techniques which lower the number of degrees of freedom will increase the efficiency of the thermodynamic sampling—provided, of course, that these techniques are physically justified. Thus, an implicit solvent model may be used to eliminate the degrees of freedom associated with the solvent molecules; the standard chemical force fields replace the electron charges with atom-centered partial charges thereby removing the electrons’ degrees 