Nonspecific interaction forces at water–membrane interface by forced molecular dynamics simulations

Nonspecific interactions are the main driving forces for the behavior of molecules with great affinity for biologic membranes. To investigate not only the molecular details of these interactions but to estimate their magnitude as well, the theoretical method of Forced Molecular Dynamics Simulations, based on the Atomic Force Spectroscopy experimental technique, was applied. In this approach, an additional one‐dimensional elastic force, representing the cantilever probe, was incorporated to the force field of a Molecular Dynamics computational program. This force represents a spring fixed on one end to a selected atom of the molecule; the other end of the spring is displaced at constant velocity to pull the molecule out of the membrane. The force experimented by the molecule due to the spring, is proportional to the spring elongation relative to its equilibrium position. This value is registered during the entire simulation, and its maximum value will determine the molecule–membrane interaction force. Nonexplicit medium simulations were carried out. Polar and apolar media were considered according to their polarizability degree and a specific dielectric constant value was assigned. In this approach, the membrane was considered as the apolar region limited by two flat surfaces with a polar aqueous medium. The potential energy discontinuity at the interfaces was smoothed by considering the polarization‐induced effects using the image method. The results of this methodology are presented using a small system, a single Alanine amino acid model, which enables extended simulations in a microsecond time scale. The confinement of this amino acid at the interface reduces its degrees of freedom and forces it to adopt one of the six defined conformations. A correlation between these stable structures at the water–membrane interface and the interaction force value was determined. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 328–339, 2003

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