Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein-protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-α-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM- GBSA calculations. Using the best RMSD among (...) the top 10 scoring poses as a metric, the success rate (RMSD ≤ 2.0 \textbackslash AA for the interface backbone atoms) increased from 21 with default Glide SP settings to 58 with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63 success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40 of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach. (shrink)

Gibt es Elemente, Bestandteile, Strukturen, die in allen Wissenschaftsbereichen, Disziplinen und Theorien fast gleich sind? Dieses Buch stellt ein neues und originelles Modell für Theorien, Theoriennetze und dynamische Entwicklungen vor, das für empirische Untersuchungen in den Sozialwissenschaften, für Computersimulationen, aber auch für praktisch-politische Anwendungen geeignet ist. Die Grundelemente in diesem Modell sind Ereignisse, Fakten, Modelle, Netze und Wahrscheinlichkeit.

R F Dearden; Theory and Practice in Education, Journal of Philosophy of Education, Volume 14, Issue 1, 30 May 2006, Pages 17–29, https://doi.org/10.1111/j.1467-.

This provocative collection of essays written by the influential Greek scholar E. R. Dodds between 1929 and 1971. represents the wide range of his literary and philosophical interests. Insightful and learned, the essays combine profound scholarship with the lucid humanity of a teacher awareof the special value of Greek studies in the modern world.

I defend the suggestion that the rational probability in the Sleeping Beauty paradox is one third. The reasoning in its favour is familiar: for every heads-waking, there are two tails-wakings. To complete the defense, I rebut the reasoning which purports to justify the competing suggestion – that the correct probability is half – by undermining its premise, that no new information has been received.

R S Downie; Professions and Professionalism, Journal of Philosophy of Education, Volume 24, Issue 2, 30 May 2006, Pages 147–159, https://doi.org/10.1111/j.1467-.

In the face of environmental crises such as climate change, pollution and biodiversity loss—which all adversely impact on health—Gils-Schmidt and Salloch explore whether physicians can be justified in taking climate issues into account in clinical care.1 While their approach centres on the ‘climate-sensitive’ decisions, physicians can carry out on the micro-level of clinical decision-making, they encourage further discussions on how climate-related issues can be included across different levels of decision-making in healthcare. We propose a list of tasks and a model (...) to assist with navigating the range of factors and structural elements an environmentally sensitive ethics must address. Stephen Gardiner’s notion of a perfect moral storm is central to understanding these issues.2 Gardiner describes how a perfect moral storm occurs in the centre of three overlapping conditions for human action and policymaking in the face of climate change. This storm is driven by: (1) a lack of interest among current generations to meet global needs and accommodate the well-being of future generations, (2) a lack of ecological concerns for other parts of nature than humans and (3) weak ethical and political theories and institutions shaping policy decisions on issues with severe implications across borders and generations. Moreover, these conditions are embedded in the existing, complex world of ethically unjustified power imbalances and social injustice. The growing awareness of healthcare’s climate footprint has amplified and accelerated global, grassroots action to make healthcare more environmentally friendly. This includes incorporating environmental impacts into quality improvement methodologies, building communities of practice to explore how to make …. (shrink)

What kind of knowledge is medical knowledge? Can medicine be explained scientifically? Is disease a scientific concept, or do explanations of disease depend on values? What is ‘evidence-based’ medicine? Are advances in neuroscience bringing us closer to a scientific understanding of the mind? The nature of medicine raises fundamental questions about explanation, causation, knowledge and ontology – questions that are central to philosophy as well as medicine. In this book Paul R. Thompson and Ross E. G. Upshur introduce the fundamental (...) issues in philosophy of medicine for those coming to the subject for the first time. They introduce and explain the following key topics: Understanding the physician-patient relationship: the phenomenology of the medical encounter. Models and theories in biology and medicine: what role do theories play in medicine? Are they similar to scientific theories? Randomised controlled trials: can scientific experiments be replicated in clinical medicine? What are the philosophical criticisms levelled at RCTs? The concept of evidence in medical research: what do we mean by ‘Evidence-based medicine?’ Should all medicine be based on evidence? Causation in medicine What do advances in neuroscience reveal about the relationship between mind and body? Defining health and disease: are explanations of disease objective or do they depend on values? Evolutionary medicine: what is the role of evolutionary biology in understanding medicine? Is it relevant? Extensive use of empirical examples and case studies is made throughout the book. These include debates about smoking and cancer, the use of placebos in randomised controlled trials and controversies about research into the causes of HIV and autism. This is an indispendable introduction to those teaching philosophy of medicine and philosophy of science. (shrink)

R W K Paterson; Towards an Axiology of Knowledge, Journal of Philosophy of Education, Volume 13, Issue 1, 30 May 2006, Pages 91–100, https://doi.org/10.1111/j.1.

The free-will defence holds that the value of significant free will is so great that God is justified in creating significantly free creatures even if there is a risk or certainty that these creatures will sin. A difficulty for the FWD, developed carefully by Quentin Smith, is that God is unable to do evil, and yet surely lacks no genuinely valuable kind of freedom. Smith argues that the kind of freedom that God has can be had by creatures, without a (...) risk of creatures doing evil. I shall show that Smith's argument fails – the case of God is disanalogous to the case of creatures precisely because creatures are creatures. (shrink)

This original and lively book explores Greek ideas about health and disease and their influence on Greek thought. Fundamental issues such as causation and responsibility, purification and pollution, mind-body relations and gender differences, authority and the expert and who can challenge them, reality and appearances, good government, happiness, and good and evil themselves are deeply implicated. Using the evidence not just from Greek medical theory and practice but also from epic, lyric, tragedy, historiography, philosophy, and religion, G. E. R. Lloyd (...) offers the first comprehensive account of the influence of Greek thought about health and disease on the Greek imagination. (shrink)

R S Downie; Professions and Professionalism, Journal of Philosophy of Education, Volume 24, Issue 2, 30 May 2006, Pages 147–159, https://doi.org/10.1111/j.1467-.

R K Elliott; Education, Love of One’s Subject, and the Love of Truth, Journal of Philosophy of Education, Volume 8, Issue 1, 30 May 2006, Pages 135–153, https:/.

R K Elliott; Education, Love of One’s Subject, and the Love of Truth, Journal of Philosophy of Education, Volume 8, Issue 1, 30 May 2006, Pages 135–153, https:/.

R K Elliott; Versions of Creativity, Journal of Philosophy of Education, Volume 5, Issue 2, 30 May 2006, Pages 139–152, https://doi.org/10.1111/j.1467-9752.1971.

R W K Paterson; Towards an Axiology of Knowledge, Journal of Philosophy of Education, Volume 13, Issue 1, 30 May 2006, Pages 91–100, https://doi.org/10.1111/j.1.

R S Peters; Education and Justification, Journal of Philosophy of Education, Volume 11, Issue 1, 30 May 2006, Pages 28–38, https://doi.org/10.1111/j.1467-9752.1.

Published here for the first time in paperback is much of a final and long-anticipated work on philosophy of history by the renowned Oxford philosopher, historian, and archaeologist R. G. Collingwood. The original text of this uncompleted work was only recently discovered in the archives of Oxford University Press. Also found there were two conclusions written by Collingwood for lectures which were eventually revised and published as The Idea of Nature, but which have relevance to his philosophy of history as (...) well. These pieces are included in this volume, accompanied by further short writings by Collingwood on historical knowledge and inquiry, selected from previously unpublished manuscripts held at the Bodleian Library, Oxford. All these writings, besides containing entirely new ideas, discuss further many of the issues which Collingwood is famous for having raised in The Idea of History and in his Autobiography.A lengthy editorial introduction sets these writings in their context, and discusses philosophical questions to which they give rise. The editors also consider why Collingwood left The Principles of History unfinished at his death, and what significance should be attached to the fact that it contains no reference to one of his best-known ideas: that of historical understanding as re-enactment. This volume will be a significant publication not just in Collingwood studies but in philosophy of history generally. (shrink)

EDITED BY SLAVENKO ŠLJUKIĆBOOK SYMPOSIUM ON KENNETH R. WESTPHAL’S HOW HUME AND KANT RECONSTRUCT NATURAL LAW.

R F Dearden; Theory and Practice in Education, Journal of Philosophy of Education, Volume 14, Issue 1, 30 May 2006, Pages 17–29, https://doi.org/10.1111/j.1467-.

R K Elliott; The Concept of Development: A Reply to Professor Hamlyn, Journal of Philosophy of Education, Volume 9, Issue 1, 30 May 2006, Pages 40–48, https://d.

R K Elliott; The Concept of Development: A Reply to Professor Hamlyn, Journal of Philosophy of Education, Volume 9, Issue 1, 30 May 2006, Pages 40–48, https://d.

R K Elliott; The Concept of Development: A Reply to Professor Hamlyn, Journal of Philosophy of Education, Volume 9, Issue 1, 30 May 2006, Pages 40–48, https://d.

R K Elliott; Versions of Creativity, Journal of Philosophy of Education, Volume 5, Issue 2, 30 May 2006, Pages 139–152, https://doi.org/10.1111/j.1467-9752.1971.

R S Peters; Education and Justification, Journal of Philosophy of Education, Volume 11, Issue 1, 30 May 2006, Pages 28–38, https://doi.org/10.1111/j.1467-9752.1.

Jonathan Dancy’s Practical Reality defends a strikingly nonpsychologistic account of motivating reasons for action. When we explain what people do by citing their reasons, we are trying to isolate the considerations that were actually effective in moving them to act. But it is crucial, Dancy contends, that these considerations be understood in a way that preserves their connection to the normative contexts in which the concept of a reason also has a place. The considerations that move agents to act are (...) considerations that agents take to cast a favorable light on the actions they perform, and it is at least sometimes the case that peoples’ motivating reasons are also good reasons for action, considerations that really do recommend or speak in favor of the action that was undertaken. If we make the plausible further assumption that these normative reasons are typically not psychological states of the agents to whom they apply, it follows that motivating reasons equally cannot be understood in essentially psychological terms. The reasons for which people act are rarely if ever psychological states to which they are subject, but facts or states of the world of the sort that are capable of counting in favor of actions, and that in successful cases render sensible or reasonable the very actions that agents in fact perform. (shrink)

R T Allen; ‘Because I Say So!’ Some Limitations Upon the Rationalisation of Authority, Journal of Philosophy of Education, Volume 21, Issue 1, 30 May 2006, Page.

R T Allen; ‘Because I Say So!’ Some Limitations Upon the Rationalisation of Authority, Journal of Philosophy of Education, Volume 21, Issue 1, 30 May 2006, Page.

R Carlisle; The Concept of Physical Education, Journal of Philosophy of Education, Volume 3, Issue 1, 30 May 2006, Pages 5–22, https://doi.org/10.1111/j.1467-97.

R F Dearden; Happiness and Education, Journal of Philosophy of Education, Volume 2, Issue 1, 30 May 2006, Pages 17–29, https://doi.org/10.1111/j.1467-9752.1968.