How do substrates enter and products exit the buried active site of cytochrome P450cam? 1. Random expulsion molecular dynamics investigation of ligand access channels and mechanisms 1 1Edited by J. Thornton

Lüdemann, Susanna K.; Lounnas, Valère; Wade, Rebecca C.

doi:10.1006/jmbi.2000.4154

Cited by 320 publications

(418 citation statements)

References 31 publications

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“…P450cam, in accordance with the earlier report 32 . The success rate of SA for this model system was 60% (three paths were predicted, including PWC).…”

Section: Cytochrome P450supporting

confidence: 93%

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Memetic algorithms for ligand expulsion from protein cavities

Rydzewski

Nowak

2015

The Journal of Chemical Physics

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Ligand diffusion through a protein interior is a fundamental process governing biological signaling and enzymatic catalysis. A complex topology of channels in proteins leads often to difficulties in modeling ligand escape pathways by classical molecular dynamics simulations. In this paper two novel memetic methods for searching the exit paths and cavity space exploration are proposed: Memory Enhanced Random Acceleration (MERA) Molecular Dynamics and Immune Algorithm (IA). In MERA, a pheromone concept is introduced to optimize an expulsion force. In IA, hybrid learning protocols are exploited to predict ligand exit paths. They are tested on three protein channels with increasing complexity: M2 muscarinic GPCR receptor, enzyme nitrile hydratase and heme-protein cytochrome P450cam. In these cases, the memetic methods outperform Simulated Annealing and Random Acceleration Molecular Dynamics. The proposed algorithms are general and appropriate in all problems where an accelerated transport of an object through a network of channels is studied.

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“…P450cam, in accordance with the earlier report 32 . The success rate of SA for this model system was 60% (three paths were predicted, including PWC).…”

Section: Cytochrome P450supporting

confidence: 93%

“…Both find plausible expulsion paths from buried receptor docking sites in three test systems: a M2 muscarinic receptor channel (M2), a biotechnological enzyme nitrile hydratase (NHase) and a cytochrome P450cam (P450cam), which has been tested in the original RAMD study by Lüdemann et al 32 (FIG. 1, 2).…”

Section: Introductionmentioning

confidence: 99%

Memetic algorithms for ligand expulsion from protein cavities

Rydzewski

Nowak

2015

The Journal of Chemical Physics

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“…Most of the computational approaches to this problem address a static view of the molecular recognition. However, several studies tend to show that the ligand access/exit to the protein active site can be very important for the understanding of the biological mechanism [25]. The difficulty is that computing the pathway of a ligand to go out from a deep active site to the surface of a protein (or vice versa) with "classic" molecular modeling methods [26] is too computationally expensive.…”

Section: B Structural Bioinformaticsmentioning

confidence: 99%

Disassembly Path Planning for Complex Articulated Objects

Cortés¹,

Siméon²

2008

IEEE Trans. Robot.

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Abstract:Sampling-based path planning algorithms are powerful tools for computing constrained disassembly motions. This paper presents a variant of the RRT algorithm particularly devised for the disassembly of objects with articulated parts. Configuration parameters generally play two different roles in this type of problems: some of them are essential for the disassembly task, while others only need to move if they hinder the progress of the disassembly process. The proposed method is based on such a partition of the configuration parameters. Results show a remarkable performance improvement compared to standard path planning techniques. The paper also shows practical applications of the presented algorithm in robotics and structural bioinformatics. Keywords:Path planning algorithms, Disassembly paths, Articulated mechanisms, Robotic manipulation, Molecular interactions. Abstract-Sampling-based path planning algorithms are powerful tools for computing constrained disassembly motions. This paper presents a variant of the RRT algorithm particularly devised for the disassembly of objects with articulated parts. Configuration parameters generally play two different roles in this type of problems: some of them are essential for the disassembly task, while others only need to move if they hinder the progress of the disassembly process. The proposed method is based on such a partition of the configuration parameters. Results show a remarkable performance improvement compared to standard path planning techniques. The paper also shows practical applications of the presented algorithm in robotics and structural bioinformatics. Submitted to IEEE Transactions of Robotics as Short Paper

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“…The estimation of correct canonical probability is inextricably associated with an efficient search for the conformational space. The rapid conformational search method (Harada et al 2015;Klvana et al 2009;Lüdemann et al 2000) can then be useful for generating initial widespread conformations although their conformations are non-equilibrated.…”

Section: Future Perspective Of Enhanced Sampling Methodsmentioning

confidence: 99%

Enhanced sampling simulations to construct free-energy landscape of protein–partner substrate interaction

2016

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Molecular dynamics (MD) simulations using allatom and explicit solvent models provide valuable information on the detailed behavior of protein-partner substrate binding at the atomic level. As the power of computational resources increase, MD simulations are being used more widely and easily. However, it is still difficult to investigate the thermodynamic properties of protein-partner substrate binding and protein folding with conventional MD simulations. Enhanced sampling methods have been developed to sample conformations that reflect equilibrium conditions in a more efficient manner than conventional MD simulations, thereby allowing the construction of accurate free-energy landscapes. In this review, we discuss these enhanced sampling methods using a series of case-by-case examples. In particular, we review enhanced sampling methods conforming to trivial trajectory parallelization, virtual-system coupled multicanonical MD, and adaptive lambda square dynamics. These methods have been recently developed based on the existing method of multicanonical MD simulation. Their applications are reviewed with an emphasis on describing their practical implementation. In our concluding remarks we explore extensions of the enhanced sampling methods that may allow for even more efficient sampling.

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How do substrates enter and products exit the buried active site of cytochrome P450cam? 1. Random expulsion molecular dynamics investigation of ligand access channels and mechanisms 1 1Edited by J. Thornton

Cited by 320 publications

References 31 publications

Memetic algorithms for ligand expulsion from protein cavities

Memetic algorithms for ligand expulsion from protein cavities

Disassembly Path Planning for Complex Articulated Objects

Enhanced sampling simulations to construct free-energy landscape of protein–partner substrate interaction

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