Izrailev

Sergei Izrailev, Sergey Stepaniants, Barry Isralewitz, Dorina Kosztin, Hui Lu, Ferenc Molnar, Willy Wriggers, and Klaus Schulten... 

Izrailev, Stepaniants, Isralewitz, Kosztin, Lu, Molnar, Wriggers, Schulten... 

The avidin-biotin complex, known for its extremely high affinity (Green, 1975), has been studied experimentally more extensively than most other protein-ligand systems. The adhesion forces between avidin and biotin have been measured directly by AFM experiments (Florin et al., 1994 Moy et al., 1994b Moy et al., 1994a). SMD simulations were performed on the entire tetramer of avidin with four biotins bound to investigate the microscopic detail of nnbinding of biotin from avidin (Izrailev et al., 1997). 

The simulations also revealed that flapping motions of one of the loops of the avidin monomer play a crucial role in the mechanism of the unbinding of biotin. The fluctuation time for this loop as well as the relaxation time for many of the processes in proteins can be on the order of microseconds and longer (Eaton et al., 1997). The loop has enough time to fluctuate into an open state on experimental time scales (1 ms), but the fluctuation time is too long for this event to take place on the nanosecond time scale of simulations. To facilitate the exit of biotin from its binding pocket, the conformation of this loop was altered (Izrailev et al., 1997) using the interactive molecular dynamics features of MDScope (Nelson et al., 1995 Nelson et al., 1996 Humphrey et al., 1996). 

In this section we describe the behavior of a ligand subjected to three types of external forces a constant force, forces exerted by a moving stiff harmonic spring, and forces exerted by a soft harmonic spring. We then present a method of reconstruction of the potential of mean force from SMD force measurements employing a stiff spring (Izrailev et al., 1997 Balsera ct al., 1997). 

Unbinding processes can be viewed as taking place in several qualitatively different regimes (Izrailev et al., 1997 Marrink et al., 1998). These regimes can be illustrated by considering the simplest binding potential... 

To unbind from a protein the ligand has to move from a, the minimum of the potential U x), to 6, the maximum of U x). The mean first passage time t F) of such motion is (Izrailev et ah, 1997)... 

The simulations of the avidin-biotin complex (Izrailev et ah, 1997) showed that a major difficulty involved in studies of the binding and flexibility of... 

Isralewitz et eil., 1997] Isralewitz, B., Izrailev, S., and Schulten, K. Binding pathway of retinal to bacterio-opsin A prediction by molecular dynamics simulations. Biophys. J. 73 (1997) 2972-2979... 

Amadei et al. 1993] Amadei, A., Linssen, A.B.M., Berendsen, H.J.C. Essential Dynamics of Proteins. Proteins 17 (1993) 412-425 [Balsera et al. 1997] Balsera, M., Stepaniants, S., Izrailev, S., Oono, Y., Schiilten, K. Reconstructing Potential Energy Functions from Simulated Force-Induced Unbinding Processes. Biophys. J. 73 (1997) 1281-1287 [Case 1996] Case, D.A. Normal mode analysis of protein dynamics. Curr. Op. Struct. Biol. 4 (1994) 285-290... 

S. Izrailev, S. Stepaniants, M. Balsera, Y. Oono, and K. Schulten. Molecular dynamics study of unbinding of the avidin-biotin complex. Biophys. J., 72 1568-1581, 1997. 

Izrailev, S. Stepaniants, S. Isralewitz, B. Kosztin, D. Lu, H. Molnar, F. Wriggers, W. Schulten, K. Steered molecular dynamics, in Computational Molecular Dynamics Challenges, Methods, Ideas, Deuflhard, P. Hermans, 1. Leimkuhler, B. Mark, A. E. Skeel, R. Reich, S., Eds., vol. 4, Lecture Notes in Computational Science and Engineering. Springer Verlag Berlin, 1998, pp. 39-65. 

In the classical case, the evolution of the kicked rotor dynamics is described by the well-known standard map (Chirikov, 1979). This map greatly facilitates the qualitative treatment of the system. A map describing the evolution of the wave function can be obtained in the quantum case, too (Casati et.al., 1979). In spite of the fact, that the first work with detailed treatment of the quantum kicked rotor appeared 23 years ago (Casati et.al., 1979), this system is still studied extensively (Casati et.al., 1987 Izrailev, 1990). 

As is well known (Chirikov, 1979 Izrailev, 1990), the phase-space evolution of the norelativistic classical kicked rotor is described by nonrelativistic standard map. The analysis of this map shows that the motion of the nonrelativistic kicked rotor is accompanied by unlimited diffusion in the energy and momentum. However, this diffusion is suppressed in the quantum case (Casati et.al., 1979 Izrailev, 1990). Such a suppression of diffusive growth of the energy can be observed when one considers the (classical) relativistic extention of the classical standard map (Nomura et.al., 1992) which was obtained recently by considering the motion of the relativistic electron in the field of an electrostatic wave packet. The relativistic generalization of the standard map is obtained recently (Nomura et.al., 1992)... 

The main feature of the quantum kicked rotor is the quantum localization phenomenon, which implies suppression of the diffusive growth of energy of the quantum kicked rotor compared to the energy of the classical rotor (Izrailev, 1990). The time dependence of the energy can be calculated as... 

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