3,803 research outputs found
A New Multi-Objective Approach for Molecular Docking Based on RMSD and Binding Energy
Ligand-protein docking is an optimization problem based on predicting the position of a ligand with the lowest binding energy in the active site of the receptor. Molecular docking problems are traditionally tackled with single-objective, as well as with multi-objective approaches, to minimize the binding energy. In this paper, we propose a novel multi-objective formulation that considers: the Root Mean Square Deviation (RMSD) difference in the coordinates of ligands and the binding (intermolecular) energy, as two objectives to evaluate the quality of the ligand-protein interactions. To determine the kind of Pareto front approximations that can be obtained, we have selected a set of representative multi-objective algorithms such as NSGA-II, SMPSO, GDE3, and MOEA/D. Their performances have been assessed by applying two main quality indicators intended to measure convergence and diversity of the fronts. In addition, a comparison with LGA, a reference single-objective evolutionary algorithm for molecular docking (AutoDock) is carried out. In general, SMPSO shows the best overall results in terms of energy and RMSD (value lower than 2A for successful docking results). This new multi-objective approach shows an improvement over the ligand-protein docking predictions that could be promising in in silico docking studies to select new anticancer compounds for therapeutic targets that are multidrug resistant.Universidad de MĂĄlaga. Campus de Excelencia Internacional AndalucĂa Tech
Ranking relations using analogies in biological and information networks
Analogical reasoning depends fundamentally on the ability to learn and
generalize about relations between objects. We develop an approach to
relational learning which, given a set of pairs of objects
,
measures how well other pairs A:B fit in with the set . Our work
addresses the following question: is the relation between objects A and B
analogous to those relations found in ? Such questions are
particularly relevant in information retrieval, where an investigator might
want to search for analogous pairs of objects that match the query set of
interest. There are many ways in which objects can be related, making the task
of measuring analogies very challenging. Our approach combines a similarity
measure on function spaces with Bayesian analysis to produce a ranking. It
requires data containing features of the objects of interest and a link matrix
specifying which relationships exist; no further attributes of such
relationships are necessary. We illustrate the potential of our method on text
analysis and information networks. An application on discovering functional
interactions between pairs of proteins is discussed in detail, where we show
that our approach can work in practice even if a small set of protein pairs is
provided.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS321 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Uncovering protein interaction in abstracts and text using a novel linear model and word proximity networks
We participated in three of the protein-protein interaction subtasks of the
Second BioCreative Challenge: classification of abstracts relevant for
protein-protein interaction (IAS), discovery of protein pairs (IPS) and text
passages characterizing protein interaction (ISS) in full text documents. We
approached the abstract classification task with a novel, lightweight linear
model inspired by spam-detection techniques, as well as an uncertainty-based
integration scheme. We also used a Support Vector Machine and the Singular
Value Decomposition on the same features for comparison purposes. Our approach
to the full text subtasks (protein pair and passage identification) includes a
feature expansion method based on word-proximity networks. Our approach to the
abstract classification task (IAS) was among the top submissions for this task
in terms of the measures of performance used in the challenge evaluation
(accuracy, F-score and AUC). We also report on a web-tool we produced using our
approach: the Protein Interaction Abstract Relevance Evaluator (PIARE). Our
approach to the full text tasks resulted in one of the highest recall rates as
well as mean reciprocal rank of correct passages. Our approach to abstract
classification shows that a simple linear model, using relatively few features,
is capable of generalizing and uncovering the conceptual nature of
protein-protein interaction from the bibliome. Since the novel approach is
based on a very lightweight linear model, it can be easily ported and applied
to similar problems. In full text problems, the expansion of word features with
word-proximity networks is shown to be useful, though the need for some
improvements is discussed
Chemoinformatics Research at the University of Sheffield: A History and Citation Analysis
This paper reviews the work of the Chemoinformatics Research Group in the Department of Information Studies at the University of Sheffield, focusing particularly on the work carried out in the period 1985-2002. Four major research areas are discussed, these involving the development of methods for: substructure searching in databases of three-dimensional structures, including both rigid and flexible molecules; the representation and searching of the Markush structures that occur in chemical patents; similarity searching in databases of both two-dimensional and three-dimensional structures; and compound selection and the design of combinatorial libraries. An analysis of citations to 321 publications from the Group shows that it attracted a total of 3725 residual citations during the period 1980-2002. These citations appeared in 411 different journals, and involved 910 different citing organizations from 54 different countries, thus demonstrating the widespread impact of the Group's work
Search algorithms as a framework for the optimization of drug combinations
Combination therapies are often needed for effective clinical outcomes in the
management of complex diseases, but presently they are generally based on
empirical clinical experience. Here we suggest a novel application of search
algorithms, originally developed for digital communication, modified to
optimize combinations of therapeutic interventions. In biological experiments
measuring the restoration of the decline with age in heart function and
exercise capacity in Drosophila melanogaster, we found that search algorithms
correctly identified optimal combinations of four drugs with only one third of
the tests performed in a fully factorial search. In experiments identifying
combinations of three doses of up to six drugs for selective killing of human
cancer cells, search algorithms resulted in a highly significant enrichment of
selective combinations compared with random searches. In simulations using a
network model of cell death, we found that the search algorithms identified the
optimal combinations of 6-9 interventions in 80-90% of tests, compared with
15-30% for an equivalent random search. These findings suggest that modified
search algorithms from information theory have the potential to enhance the
discovery of novel therapeutic drug combinations. This report also helps to
frame a biomedical problem that will benefit from an interdisciplinary effort
and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio
Paradigms for computational nucleic acid design
The design of DNA and RNA sequences is critical for many endeavors, from DNA nanotechnology, to PCRâbased applications, to DNA hybridization arrays. Results in the literature rely on a wide variety of design criteria adapted to the particular requirements of each application. Using an extensively studied thermodynamic model, we perform a detailed study of several criteria for designing sequences intended to adopt a target secondary structure. We conclude that superior design methods should explicitly implement both a positive design paradigm (optimize affinity for the target structure) and a negative design paradigm (optimize specificity for the target structure). The commonly used approaches of sequence symmetry minimization and minimum freeâenergy satisfaction primarily implement negative design and can be strengthened by introducing a positive design component. Surprisingly, our findings hold for a wide range of secondary structures and are robust to modest perturbation of the thermodynamic parameters used for evaluating sequence quality, suggesting the feasibility and ongoing utility of a unified approach to nucleic acid design as parameter sets are refined further. Finally, we observe that designing for thermodynamic stability does not determine folding kinetics, emphasizing the opportunity for extending design criteria to target kinetic features of the energy landscape
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