Volume-based solvation models out-perform area-based models in combined studies of wild-type and mutated protein-protein interfaces

<p>Abstract</p> <p>Background</p> <p>Empirical binding models have previously been investigated for the energetics of protein complexation (ΔG models) and for the influence of mutations on complexation (i.e. differences between wild-type and mutant complexes, ΔΔG models). We construct binding models to directly compare these processes, which have generally been studied separately.</p> <p>Results</p> <p>Although reasonable fit models were found for both ΔG and ΔΔG cases, they differ substantially. In a dataset curated for the absence of mainchain rearrangement upon binding, non-polar area burial is a major determinant of ΔG models. However this ΔG model does not fit well to the data for binding differences upon mutation. Burial of non-polar area is weighted down in fitting of ΔΔG models. These calculations were made with no repacking of sidechains upon complexation, and only minimal packing upon mutation. We investigated the consequences of more extensive packing changes with a modified mean-field packing scheme. Rather than emphasising solvent exposure with relatively extended sidechains, rotamers are selected that exhibit maximal packing with protein. This provides solvent accessible areas for proteins that are much closer to those of experimental structures than the more extended sidechain regime. The new packing scheme increases changes in non-polar burial for mutants compared to wild-type proteins, but does not substantially improve agreement between ΔG and ΔΔG binding models.</p> <p>Conclusion</p> <p>We conclude that solvent accessible area, based on modelled mutant structures, is a poor correlate for ΔΔG upon mutation. A simple volume-based, rather than solvent accessibility-based, model is constructed for ΔG and ΔΔG systems. This shows a more consistent behaviour. We discuss the efficacy of volume, as opposed to area, approaches to describe the energetic consequences of mutations at interfaces. This knowledge can be used to develop simple computational screens for binding in comparative modelled interfaces.</p

Soil properties under Amazon forest and changes due to pasture installation in Rondônia, Brazil Soil properties under Amazon forest and changes due to pasture installation in Rondônia, Brazil

Scope of the journal The primary intention of the journal is to stimulate wide interdisciplinary cooperation and understanding among workers in the different fields of pedology. Therefore, the journal tries to bring together papers from the entiire field of soil research, rather than to emphasize any one subdiscipline. Interdisciplinary work should preferably be focused on occurrence and dynamic charactlerizatiorn in space and time of soils in the field. Publication information Geoderma . For 1996 volumes 69-74 are sclheduled for publication. Subscription prices are available upon request from the publisher. Subscriptions are accepted on a prepaid basis only ar;d are entered on a calendar year basis. Issues are sent by surface mail except to the following countries where air delivery via SAL is ensured: Argentina, Australia, Brazil, Canada, Hong Kong, India, Israel, Japan, Malaysia, Mexico, New Zealand, Pakistan, PR China, Singapore, South Africa, South Korea, Taiwan, Thailand, USA. For all other countries airmail rates are available upon request. Claims for missing issues must be made within six months of our publication Abstract We examined the consequences of deforestation and pasture establishment for soil chemical and physical properties and for soil organic matter content, in Rondônia, in the southwestem part of the Brazilian Amazon basin. Two chronosequences were selected. One chronosequence consisted of a forest and pasture established in 1989, 1987, 1983, 1979 and 1972. The main soil type in this area is the red yellow podzolic latosol (Kandiudult). The second chronosequence consisted of a forest site and pasture established in 1987, 1983, 1972 and 1911, and the main soil type is a red yellow podzolic soil (Paleudult, Tropudult). The first soil type is the most base-depleted soil and has a higher clay content than the second one. Despite the initial differences in clay and cations contents between the forest sites the total soil carbon content at 0-30 cm in both forest were circa 3.7 kg C m-*. After pasture installation soil bulk density were higher in the first 0-5 cm soil layer, mainly in one chronosequence but small changes were detected in deeper soil layers. Forest&apos;conversion to pasture caused appreciable increases in soil pH and exchangeable cation content, at least until nine years after pasture installation. pH levels were greater in the first chronosequence, with highest values (6.8 to 7.6) found in 3 and 5 years old pastures respectively. In the most base-depleted soil Ca content increased from 0.07 kg m-2 in the forest site to 0.25 kg m-2 in the 5 year old pasture. After normalization by clay content total soil carbon contents to 30 cm in the 20 year old pastures were 17 to 20% higher than in the original forest sites. Calculations of carbon derived from forest (Cdf) and from pasture (Cdp) using soil 6I3C values showed that Cdf decrease sharply in the first 9 years after pasture establishment in both chronosequences and reached stable values of 2.12 kg C m -2 and 2.02 kg C mb2 in chronosequences 1 and 2,, respectively. Soil carbon derived from pasture increased with time and represented 50% of total (1996) 63-81 soil carbon in the top 30 cm after 20 years of pasture. In general we observed that forest conversion to pasture is associated to a pattern of increasing of soil cations and pH levels for at least 5 years under pasture establishment. The removal of the original forest for pasture establishment resulted in an accumulation of carbon derived from pasture in the soil

Nitrate leaching through oxisols of the Loyalty Islands (New Caledonia) under intensified agricultural practices. Geoderma

Scope of the journal The primary intention of the journal is to stimulate wide interdisciplinary cooperation and understanding among workers in the different fields of pedology. Therefore, the journal tries to bring together papers from the entire field of soil research, rather than to emphasize any one subdiscipline. Interdisciplinary work should preferably be focused on occurrence and dynamic characterization in space and time of soils in the field. . For 1998 volumes 81-86 are scheduled for publication. Subscription prices are available upon request from the publisher. Subscriptions are accepted on a prepaid basis only and are entered on a calendar year basis. Issues are sent by surface mail except to the following countries where air delivery via SAL is ensured: Argentina, Australia, Brazil, Canada, Hong Kong, India, Israel, Japan, Malaysia, Mexico, New Zealand, Pakistan, PR China, Singapore, South Africa, South Korea, Taiwan, Thailand, USA. For all other countries airmail rates are available upon request. Claims for missing issues must be made within six months of our publication (mailing) date. For orders, claims, product enquiries (no manuscript enquiries) please contact Customer Support Department at the Regional Sales Office nearest to you: Publication information G E O D E W ELSEVIER Abstract For the uplifted coral atolls of the Loyalty Islands (New Caledonia), the prime source of potable water is the freshwater lenses that underlie the islands. The recent adoption of more-intensive agricultural practices, particularly the use of nitrogeneous fertilizers, may, however, represent a threat for these fragile Pacific ecosystems. To assess the risk posed by nitrate leaching, experiments have been conducted on the permeable oxisols of the island of Maré, using both cropped and bare soil sites. Drainage below the root zone was found to be very important, about 50% of the rainfall, even on the cropped site. The soils are thin and permeable, and the frequent tropical storms have high rainfall intensities. Nitrate fertilizers thus have potential to be leached, in large amounts, even up to 100% of the nitrate supply, especially if fertilizers are not supplied according to weather conditions and in concert with the plant&apos;s ability to extract them. O 1998 Elsevier Science B.V. All rights reserved

Pharmacogenetics of the g protein-coupled receptors

Pharmacogenetics investigates the influence of genetic variants on physiological phenotypes related to drug response and disease, while pharmacogenomics takes a genome-wide approach to advancing this knowledge. Both play an important role in identifying responders and nonresponders to medication, avoiding adverse drug reactions, and optimizing drug dose for the individual. G protein-coupled receptors (GPCRs) are the primary target of therapeutic drugs and have been the focus of these studies. With the advance of genomic technologies, there has been a substantial increase in the inventory of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms and insertion or deletions that have potential to alter GPCR expression of function. In vivo and in vitro studies have determined functional roles for many GPCR variants, but genetic association studies that define the physiological impact of the majority of these common variants are still limited. Despite the breadth of pharmacogenetic data available, GPCR variants have not been included in drug labeling and are only occasionally considered in optimizing clinical use of GPCR-targeted agents. In this chapter, pharmacogenetic and genomic studies on GPCR variants are reviewed with respect to a subset of GPCR systems, including the adrenergic, calcium sensing, cysteinyl leukotriene, cannabinoid CB1 and CB2 receptors, and the de-orphanized receptors such as GPR55. The nature of the disruption to receptor function is discussed with respect to regulation of gene expression, expression on the cell surface (affected by receptor trafficking, dimerization, desensitization/downregulation), or perturbation of receptor function (altered ligand binding, G protein coupling, constitutive activity). The large body of experimental data generated on structure and function relationships and receptor-ligand interactions are being harnessed for the in silico functional prediction of naturally occurring GPCR variants. We provide information on online resources dedicated to GPCRs and present applications of publically available computational tools for pharmacogenetic studies of GPCRs. As the breadth of GPCR pharmacogenomic data becomes clearer, the opportunity for routine assessment of GPCR variants to predict disease risk, drug response, and potential adverse drug effects will become possible