Topic
Molecular binding
About: Molecular binding is a research topic. Over the lifetime, 256 publications have been published within this topic receiving 7211 citations.
Papers published on a yearly basis
Papers
TL;DR: It is suggested that the class of pocket dynamics, as well as the type and extent of protein motion affecting the binding pocket, should be factors considered in choosing the most appropriate computational approach to study a given binding pocket.
Abstract: The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five different classes of protein pocket dynamics: (1) appearance/disappearance of a subpocket in an existing pocket; (2) appearance/disappearance of an adjacent pocket on the protein surface in the direct vicinity of an already existing pocket; (3) pocket breathing, which may be caused by side-chain fluctuations or backbone or interdomain vibrational motion; (4) opening/closing of a channel or tunnel, connecting a pocket inside the protein with solvent, including lid motion; and (5) the appearance/disappearance of an allosteric pocket at a site on a protein distinct from an already existing pocket with binding of a ligand to the allosteric binding site affecting the original pocket. We suggest that the class of pocket dynamics, as well as the type and extent of protein motion affecting the binding pocket, should be factors considered in choosing the most appropriate computational approach to study a given binding pocket. Furthermore, we examine the relationship between pocket dynamics classes and induced fit, conformational selection, and gating models of ligand binding on binding kinetics and thermodynamics. We discuss the implications of protein binding pocket dynamics for drug design and conclude with potential future directions for computational analysis of protein binding pocket dynamics.
363 citations
TL;DR: This work is a review of the Poisson–Boltzmann (PB) continuum electrostatics theory and its modifications, with a focus on salt effects and counterion binding, and discusses the conventional PB equation, the corresponding functionals of the electrostatic free energy, including a connection to DFT.
Abstract: This work is a review of the Poisson-Boltzmann (PB) continuum electrostatics theory and its modifications, with a focus on salt effects and counterion binding. The PB model is one of the mesoscopic theories that describes the electrostatic potential and equilibrium distribution of mobile ions around molecules in solution. It serves as a tool to characterize electrostatic properties of molecules, counterion association, electrostatic contributions to solvation, and molecular binding free energies. We focus on general formulations which can be applied to large molecules of arbitrary shape in all-atomic representation, including highly charged biomolecules such as nucleic acids. These molecules present a challenge for theoretical description, because the conventional PB model may become insufficient in those cases. We discuss the conventional PB equation, the corresponding functionals of the electrostatic free energy, including a connection to DFT, simple empirical extensions to this model accounting for finite size of ions, the modified PB theory including ionic correlations and fluctuations, the cell model, and supplementary methods allowing to incorporate site-bound ions in the PB calculations.
330 citations
TL;DR: Several possible optical and photophysical effects that can influence the outcome of a FCS measurement and thus can bias the value of the derived diffusion coefficient are discussed.
Abstract: Fluorescence correlation spectroscopy (FCS) is an important technique for studying low concentrations of analyte molecules in solution. The core molecular characteristic that can be addressed by FCS is the translational diffusion coefficient of the analyte molecules, which can be used for i.e. studying molecular binding and reactions, or conformational changes of macromolecules. The present paper discusses several possible optical and photophysical effects that can influence the outcome of a FCS measurement and thus can bias the value of the derived diffusion coefficient.
230 citations
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TL;DR: Cooperative binding occurs when the number of binding sites of a macromolecule that are occupied by a specific type of ligand is a nonlinear function of this ligand's concentration as mentioned in this paper.
Abstract: Molecular binding is an interaction between molecules that results in a stable association between those molecules. Cooperative binding occurs if the number of binding sites of a macromolecule that are occupied by a specific type of ligand is a nonlinear function of this ligand's concentration. This can be due, for instance, to an affinity for the ligand that depends on the amount of ligand bound. Cooperativity can be positive (supralinear) or negative (infralinear). Cooperative binding is most often observed in proteins, but nucleic acids can also exhibit cooperative binding, for instance of transcription factors. Cooperative binding has been shown to be the mechanism underlying a large range of biochemical and physiological processes.
202 citations
2 Oct 1993
TL;DR: It is shown that the DNA size distribution, as well as the activities of nuclease, can be determined by the measurement of the apparent length of stretched DNA.
Abstract: The authors have previously reported that the electrostatic orientation and the dielectrophoresis (DEP) of DNA occur under /spl ap/1 MHz, >1/spl times/10/sup 6/ V/m field, by which DNA strands are stretched straight along field lines and positioned onto electrode edges. This paper presents some application of this stretch-and-positioning method to genetic engineering. It is shown that the DNA size distribution, as well as the activities of nuclease, can be determined by the measurement of the apparent length of stretched DNA. Several methods are developed to immobilize stretched DNA onto a substrate, including: (1) immobilization onto a conducting substrate for observations with the scanning tunneling microscopy, (2) anchoring onto a substrate only at both ends of the DNA using special electrode configuration, and/or molecular binding between avidin and biotin. The DNA can be held without contact to the substrate in the latter method, so that it does not cause steric hindrances to the DNA-binding enzymes. A novel fluid integrated circuit (FIC) device is proposed in which stretched DNA is cut by laser beam for the successive sequencing. A method to obtain unidirectionally oriented DNA is developed. The spatial resolution, and the small number of molecules required, are the advantages of the assays and measurements using electrostatic DNA manipulations over conventional biochemical methods. It is hoped that the methods may open a way to a novel category of "molecular biochemistry with spatial resolution.". >
181 citations
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| Year | Papers |
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| 2025 | 1 |
| 2024 | 2 |
| 2023 | 13 |
| 2022 | 20 |
| 2021 | 13 |
| 2020 | 16 |