The waters of life
01 Mar 1998-Journal of The Franklin Institute-engineering and Applied Mathematics (Pergamon)-Vol. 335, Iss: 2, pp 213-240
TL;DR: The main difficulty in understanding solvation phenomena arises from the effects of electrostatics in complex biomolecular systems as discussed by the authors, and the fundamental concepts and methodologies in evaluating electrostatic contributions to solvation.
Abstract: Water serves as a critical solvent for a remarkable array of molecules; in particular it profoundly influences the structure and activity of proteins, and their molecular interactions. Our ability to understand biological processes and to develop innovative applications for biotechnology depend in large part on understanding the biophysics of proteins in their solvated environment. The main difficulty in understanding solvation phenomena arises from the effects of electrostatics in complex biomolecular systems. In this paper we survey and critique the fundamental concepts and methodologies in evaluating electrostatic contributions to solvation.
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TL;DR: This paper proposes a rethinking of socio-economic development from resource-based to knowledge-based; from exogenous to endogenous; from state-led to university-led; and from single or double institutional effort to triple helix interaction.
Abstract: This paper proposes a rethinking of socio-economic development from resource-based to knowledge-based; from exogenous to endogenous; from state-led to university-led; and from single or double institutional effort to triple helix interaction. The triple helix development model seeks to create robust university, industry and government spheres, enhance interaction capabilities through the ability of individuals to circulate from one sphere to another. This task can be accomplished through two strategic action plans. In the first instance, there is the need for the development of an entrepreneurial university and/or enhancing academic capabilities, by drawing in persons from industry and government. Second, there is the need to encourage the circulation of elites among university–industry–government in less developed countries characterised by strong, but largely inefficient governments, the relative low industrial capacity and weak academic sectors dominated by government. The triple helix model is applica...
78 citations
TL;DR: The analysis uncovers energy gradients, or funnels, near the binding site, with decreasing energy as the degree of similarity between the native and docked structures increases, which could provide an explanation for the relatively rapid association rates that are observed even in the absence of long‐range electrostatic steering.
Abstract: We present a rapidly executable minimal binding energy model for molecular docking and use it to explore the energy landscape in the vicinity of the binding sites of four different enzyme inhibitor complexes. The structures of the complexes are calculated starting with the crystal structures of the free monomers, using DOCK 4.0 to generate a large number of potential configurations, and screening with the binding energy target function. In order to investigate possible correlations between energy and variation from the native structure, we introduce a new measure of similarity, which removes many of the difficulties associated with root mean square deviation. The analysis uncovers energy gradients, or funnels, near the binding site, with decreasing energy as the degree of similarity between the native and docked structures increases. Such energy funnels can increase the number of random collisions that may evolve into productive stable complex, and indicate that short-range interactions in the precomplexes can contribute to the association rate. The finding could provide an explanation for the relatively rapid association rates that are observed even in the absence of long-range electrostatic steering.
70 citations
01 Dec 2006
TL;DR: In the context of New Zealand's Action Plan for Sustainable Development (APSD) as discussed by the authors, cultural effects are considered in four dimensions: social, economic, environmental and cultural effects of decisions.
Abstract: Sustainability legislation in New Zealand (NZ) provides an interesting challenge for decision-makers such as planners, architects and engineers. NZ's Action Plan for Sustainable Development requires ‘taking account of the social, economic, environmental and cultural effects of our decisions’. The assessment of sustainability in NZ thus occurs in four dimensions. Internationally, cultural effects are generally considered within the analysis of societal effects. The separate consideration of cultural effects is necessary in NZ to acknowledge the status of the indigenous people, the Tangata Whenua. The requirement for separate consideration of cultural effects was created in NZ's founding document, the 1840 Treaty of Waitangi. Although the addition of a cultural criterion to decisionsupport tools (DSTs) could be considered a viable solution to accommodate the partnership obligations created by the Treaty, the extension of international sustainability DSTs in this way has not worked in practice. The acknowled...
56 citations
Cites background from "The waters of life"
...Indigenous management of the environment is carried out for a water catchment by the hapū (clan group).(6) The importance of regional approaches for water management has been acknowledged in the system dynamics field by Simonovic,(7) who identified the significance of water pollution at a global level, but noted that solutions for water problems are on a regional level....
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01 Jan 2007
TL;DR: The transformation of higher educational institutions, in particular universities, whether through internal or external impetuses from a teaching to a research and to an entrepreneurial university is a key element in creating a viable triple helix as mentioned in this paper.
Abstract: A stable regulatory framework for knowledge-based societies is a necessary but not sufficient condition for organizational innovation. The transformation of higher educational institutions, in particular universities, whether through internal or external impetuses from a teaching to a research and to an entrepreneurial university is a key element in creating a viable triple helix. Government actor’s focus on innovation as well as traditional government activities is also a prerequisite. If knowledge-based industries are lacking; universitygovernment interactions can help jump-start their creation. We argue that for Africa to integrate itself into the global knowledge economy, its development agenda should be organized around reinvigorated higher educational institutions that foster triple helix interactions.
36 citations
TL;DR: The surface of active polarons (SOAP) as discussed by the authors was proposed for solvating biomolecules in molecular dynamics or Monte Carlo simulations, which employs a thin layer (often monomolecular) of explicit water with additional external forces representing the electrostatics, pressure, fluctuations and dissipations caused by the neglected bulk.
Abstract: We present a strategy for solvating biomolecules in molecular dynamics or Monte Carlo simulations. The method employs a thin layer (often monomolecular) of explicit water with additional external forces representing the electrostatics, pressure, fluctuations, and dissipations caused by the neglected bulk. Long-range electrostatic corrections are supplied through a set of variable surface charges (polarons) that recreates the mean reaction field (or dielectric properties) of an infinite solvent. We refer to this “fictitious” boundary layer as a “surface of active polarons” (or SOAP). Test simulations of the solvation free energies of 15 amino acid analogs and nine ions are in good agreement with experiment (correlation coefficients: 0.995 and 1.000, respectively) despite the use of unaltered published force-fields with only one adjustable parameter. Dynamical capabilities of SOAP are illustrated by application to a six residue peptide with a stable conformation (SYPFDV), as well as a flexible nine residue HIV-1 gp120 peptide (TLTSCNTSV from PDB 1hhg). Future extensions, calibrations, and applications are discussed briefly.
18 citations
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TL;DR: The CHARMM (Chemistry at Harvard Macromolecular Mechanics) as discussed by the authors is a computer program that uses empirical energy functions to model macromolescular systems, and it can read or model build structures, energy minimize them by first- or second-derivative techniques, perform a normal mode or molecular dynamics simulation, and analyze the structural, equilibrium, and dynamic properties determined in these calculations.
Abstract: CHARMM (Chemistry at HARvard Macromolecular Mechanics) is a highly flexible computer program which uses empirical energy functions to model macromolecular systems. The program can read or model build structures, energy minimize them by first- or second-derivative techniques, perform a normal mode or molecular dynamics simulation, and analyze the structural, equilibrium, and dynamic properties determined in these calculations. The operations that CHARMM can perform are described, and some implementation details are given. A set of parameters for the empirical energy function and a sample run are included.
14,725 citations
TL;DR: The Protein Data Bank is a computer-based archival file for macromolecular structures that stores in a uniform format atomic co-ordinates and partial bond connectivities, as derived from crystallographic studies.
7,983 citations
TL;DR: The accessibility of atoms in the twenty common amino acids in model tripeptides of the type Ala-X-Ala are given for defined conformation and the larger non-polar amino acids tend to be more “buried” in the native form of all three proteins.
5,697 citations
TL;DR: It is demonstrated in this work that the surface tension, water‐organic solvent, transfer‐free energies and the thermodynamics of melting of linear alkanes provide fundamental insights into the nonpolar driving forces for protein folding and protein binding reactions.
Abstract: We demonstrate in this work that the surface tension, water-organic solvent, transfer-free energies and the thermodynamics of melting of linear alkanes provide fundamental insights into the nonpolar driving forces for protein folding and protein binding reactions. We first develop a model for the curvature dependence of the hydrophobic effect and find that the macroscopic concept of interfacial free energy is applicable at the molecular level. Application of a well-known relationship involving surface tension and adhesion energies reveals that dispersion forces play little or no net role in hydrophobic interactions; rather, the standard model of disruption of water structure (entropically driven at 25 degrees C) is correct. The hydrophobic interaction is found, in agreement with the classical picture, to provide a major driving force for protein folding. Analysis of the melting behavior of hydrocarbons reveals that close packing of the protein interior makes only a small free energy contribution to folding because the enthalpic gain resulting from increased dispersion interactions (relative to the liquid) is countered by the freezing of side chain motion. The identical effect should occur in association reactions, which may provide an enormous simplification in the evaluation of binding energies. Protein binding reactions, even between nearly planar or concave/convex interfaces, are found to have effective hydrophobicities considerably smaller than the prediction based on macroscopic surface tension. This is due to the formation of a concave collar region that usually accompanies complex formation. This effect may preclude the formation of complexes between convex surfaces.
5,295 citations