Microsecond Scale Replica Exchange Molecular Dynamic Simulation of Villin Headpiece: An Insight into the Folding Landscape

Abstract

Reaching the experimental time scale of millisecond is a grand challenge for protein folding simulations. The development of advanced Molecular Dynamics techniques like Replica Exchange Molecular Dynamics (REMD) makes it possible to reach these experimental timescales. In this study, an attempt has been made to reach the multi microsecond simulation time scale by carrying out folding simulations on a three helix bundle protein, Villin, by combining REMD and Amber United Atom model. Twenty replicas having different temperatures ranging from 295 K to 390 K were simulated for 1.5 μs each. The lowest Root Mean Square Deviation (RMSD) structure of 2.5 Å was obtained with respect to native structure (PDB code 1VII), with all the helices formed. The folding population landscapes were built using segment-wise RMSD and Principal Components as reaction coordinates. These analyses suggest the two-stage folding for Villin. The combination of REMD and Amber United Atom model may be useful to understand the folding mechanism of various fast folding proteins     

Middle Pleistocene ecology and Neanderthal subsistence: Insights from stable isotope analyses in Payre (Ardèche,southeastern France)

The Middle Palaeolithic site of Payre in southeastern France yields abundant archaeological material associated with fossil hominid remains. With its long sequence of Middle Pleistocene deposits, Payre is a key site to study the Middle Palaeolithic chronology of this region. This study is the first to investigate carbon and oxygen isotope contents of Neanderthal tooth enamel bioapatite, together with a wide range of herbivorous and carnivorous species. The aim is to contribute to the understanding of hunting behaviour, resource partitioning, diet and habitat use of animals and Neanderthals through a palaeoecological reconstruction.     

Norms in the politics of housing for minorities: Evidence from a French,a German and a US metropolitan area

Throughout Western societies, policy‐makers who address the problems of disadvantaged ethnic and immigrant minorities confront norms that prescribe equal or preferential treatment for these groups. Variations in these norms make significant differences in policy‐making. Based on evidence from housing and planning policies and a standardized survey of local élites in comparable German, French and US metropolitan areas, this article analyses how these norms altered logics of policy‐making. Normative differences help to explain why policies to house minorities proved more successful in the German setting than in the French. Contrasts in central‐local relations, in local government, in political parties and in the social and economic background of policy‐making fail to account for the difference that these norms make. In the American setting normative ambiguities combined with institutional, social and spatial differences to render parallel norms comparatively ineffective.     

On race: 34 conversations in a time of crisis

The purpose of this Research Note is to offer an analysis of the goals and achievements of former President Clinton's Initiative on Race from its announcement in June 1997 through spring 2000. This Initiative was the first attempt in nearly thirty years by a United States' President to seriously and systematically address the issue of "race". Three conclusions emerge: first, the Clinton Race Initiative accomplished more than most social scientists and the public are aware of; second, the Initiative is incomplete because the President has not released his own proposed book-length analysis on race; and, third, a number of structural and political factors significantly limited the "success" of the Initiative.     

The Position of the United States on the Northwest Passage: Is the Fear of Creating a Precedent Warranted?

For decades, Ottawa and Washington have been agreeing to disagree on the question of the legal status of the Northwest Passage. One argument which has been consistently raised on the U.S. side and which has precluded attempts to end the deadlock has been the fear of creating a negative precedent. This article assesses whether U.S. concerns are warranted: could coastal States elsewhere in the world rely on an eventual recognition of Canadian sovereignty over the Northwest Passage to bolster their claims over a local strait?     

Law of the Sea Issues Between the United States and East Asian States

The United States is the sole superpower in the contemporary world and its role in the development of the law of the sea cannot be ignored. Although having not yet acceded to the U.N. Convention on the Law of the Sea, the United States has contributed to the development of the international law of the sea in numerous ways, including responding to the so-called excessive maritime claims in East Asia and creating new rules of maritime enforcement. This article assesses this recent U.S. practice.     

Maritime Legislation of Mainland China and Taiwan: Developments,Comparison, Implications,and Potential Challenges for the United States

In January 1998, Taiwan promulgated the Law of the Republic of China (ROC) on the Territorial Sea and the Contiguous Zone and the Law of the Republic of China on the Exclusive Economic Zone (EEZ) and the Continental Shelf, both of which came into force on January 21, 1998. On June 26, 1998, China adopted the Law of the People's Republic of China on the Exclusive Economic Zone and the Continental Shelf, which is the most significant maritime legislation since its 1992 Law on the Territorial Sea and the Contiguous Zone. This article studies the recent maritime legislation developments in Mainland China and Taiwan, the differences and similarities between the two sets of laws, their implications for the Asia-Pacific region, and the potential challenges for the United States.     

The case in international law for Canada's extension of fisheries jurisdiction beyond 200 miles

In March 1995, Canadian fisheries authorities boarded and arrested the Spanish fishing vessel, Estai, outside the Canadian 200‐mile zone on the Grand Banks, an event that served to focus world attention on a dispute that had its origins in the failure of the 1982 United Nations Convention on the Law of the Sea to implement an effective conservation and management regime for fish stocks on the high seas, particularly with respect to fish stocks that straddle coastal states’ exclusive economic zones. This article examines the origins of the dispute, including the allegations relating to overfishing of North Atlantic Fisheries Organization‐recommended quotas, the background to the vessel's arrest, and the subsequent confrontation that occurred, both at diplomatic levels and on the high seas, between Canada and the European Union. An analysis is made of the case in international law for Canada's extension of jurisdiction beyond 200 miles pursuant to the provisions of Section 5 of the Coastal Fisheries Protection Act. Finally, the article examines the implications of the recently concluded Agreement on the Conservation and Management of Straddling Fish Stocks and Highly Migratory Fish Stocks for disputes of the kind that arose in the present case.     

Living standards and inequality in the industrial revolution: Evidence from the height of University of Edinburgh students in the 1830s

Trends in living standards during the Industrial Revolution is a core debate in economic history. Studies using anthropometric records from institutional sources have found downward trends in living standards during the first half of the nineteenth century. This paper contributes to this literature by utilising an overlooked source of middle and upper class anthropometric data: the height and weight of university students. Combined with more traditional anthropometric sources these data give us a snapshot into the range of living standards experienced by different sections of society in the United Kingdom. Our findings suggest that inequality was most pronounced in Ireland, followed by England. Height inequality in Scotland was still substantial, but somewhat lower in comparison.