Author
Russell F. Doolittle
Other affiliations: Amherst College, Harvard University, University of California, Los Angeles ...read more
Bio: Russell F. Doolittle is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Peptide sequence & Fibrin. The author has an hindex of 80, co-authored 284 publications receiving 47974 citations. Previous affiliations of Russell F. Doolittle include Amherst College & Harvard University.
Topics: Peptide sequence, Fibrin, Amino acid, Thrombin, Fibrinogen
Papers published on a yearly basis
Papers
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TL;DR: A computer program that progressively evaluates the hydrophilicity and hydrophobicity of a protein along its amino acid sequence has been devised and its simplicity and its graphic nature make it a very useful tool for the evaluation of protein structures.
21,921 citations
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TL;DR: A progressive alignment method that utilizes the Needleman and Wunsch pairwise alignment algorithm iteratively to achieve the multiple alignment of a set of protein sequences and to construct an evolutionary tree depicting their relationship is described.
Abstract: A progressive alignment method is described that utilizes the Needleman and Wunsch pairwise alignment algorithm iteratively to achieve the multiple alignment of a set of protein sequences and to construct an evolutionary tree depicting their relationship. The sequences are assumed a priori to share a common ancestor, and the trees are constructed from difference matrices derived directly from the multiple alignment. The thrust of the method involves putting more trust in the comparison of recently diverged sequences than in those evolved in the distant past. In particular, this rule is followed: “once a gap, always a gap”. The method has been applied to three sets of protein sequences: 7 superoxide dismutases, 11 globins, and 9 tyrosine kinase-like sequences. Multiple alignments and phylogenetic trees for these sets of sequences were determined and compared with trees derived by conventional pairwise treatments. In several instances, the progressive method led to trees that appeared to be more in line with biological expectations than were trees obtained by more commonly used methods.
2,014 citations
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TL;DR: The demonstrating of extensive sequence similarity between the transforming protein derived from the simian sarcoma virus onc gene, v-sis, and a human platelet-derived growth factor shows that this protein could be a factor active transiently during normal cell growth.
Abstract: The transforming protein of a primate sarcoma virus and a platelet-derived growth factor are derived from the same or closely related cellular genes. This conclusion is based on the demonstration of extensive sequence similarity between the transforming protein derived from the simian sarcoma virus onc gene, v-sis, and a human platelet-derived growth factor. The mechanism by which v-sis transforms cells could involve the constitutive expression of a protein with functions similar or identical to those of a factor active transiently during normal cell growth.
1,415 citations
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TL;DR: The systemic comparison of every newly determined amino acid sequence with all other known sequences may allow a complete reconstruction of the evolutionary events leading to contemporary proteins, but sometimes the surviving similarities are so vague that even computer-based sequence comparisons procedures are unable to validate relationships.
Abstract: The systemic comparison of every newly determined amino acid sequence with all other known sequences may allow a complete reconstruction of the evolutionary events leading to contemporary proteins. But sometimes the surviving similarities are so vague that even computer-based sequence comparisons procedures are unable to validate relationships. In other cases similar sequences may appear in totally alien proteins as a result of mere chance or, occasionally, by the convergent evolution of sequences with special properties.
793 citations
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TL;DR: At Atomic-level details are now in hand for many of the interactions that hold fibrin units together, although some aspects have yet to be resolved.
Abstract: Fibrinogen is a soluble plasma protein that is converted to polymeric fibrin in response to damage to the vascular system The clotting process is initiated when platelets aggregate at the wound site Their disruption releases biologically active amines and a proteolytic cascade follows which culminates in the conversion of fibrinogen to fibrin The fibrin polymer forms the matrix of the tangle of cellular and molecular substances called the blood clot Atomic-level details are now in hand for many of the interactions that hold fibrin units together, although some aspects have yet to be resolved Of necessity, fibrin clots need to be dismantled when they are no longer needed, an operation largely accomplished by the proteolytic enzyme plasmin Various regulatory phenomena are involved in maintaining the balance between intravascular fluidity and clots that prevent blood loss A variety of hereditary conditions, including mutant fibrinogens, can predispose individuals to either thrombosis or bleeding
Key concepts:
The underlying fabric of blood clots is a protein polymer called fibrin
Fibrin clots are formed in response to injuries to any part of the vascular system
The conversion of soluble fibrinogen molecules to insoluble fibrin depends on thrombin generated from prothrombin
Keywords:
fibrinogen;
fibrin;
clot stabilisation;
fibrinolysis;
blood clotting;
X-ray structures
716 citations
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TL;DR: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved and modifications are incorporated into a new program, CLUSTAL W, which is freely available.
Abstract: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.
63,427 citations
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TL;DR: ClUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W, providing an integrated system for performing multiple sequence and profile alignments and analysing the results.
Abstract: CLUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W. The new system is easy to use, providing an integrated system for performing multiple sequence and profile alignments and analysing the results. CLUSTAL X displays the sequence alignment in a window on the screen. A versatile sequence colouring scheme allows the user to highlight conserved features in the alignment. Pull-down menus provide all the options required for traditional multiple sequence and profile alignment. New features include: the ability to cut-and-paste sequences to change the order of the alignment, selection of a subset of the sequences to be realigned, and selection of a sub-range of the alignment to be realigned and inserted back into the original alignment. Alignment quality analysis can be performed and low-scoring segments or exceptional residues can be highlighted. Quality analysis and realignment of selected residue ranges provide the user with a powerful tool to improve and refine difficult alignments and to trap errors in input sequences. CLUSTAL X has been compiled on SUN Solaris, IRIX5.3 on Silicon Graphics, Digital UNIX on DECstations, Microsoft Windows (32 bit) for PCs, Linux ELF for x86 PCs, and Macintosh PowerMac.
38,522 citations
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TL;DR: MUSCLE is a new computer program for creating multiple alignments of protein sequences that includes fast distance estimation using kmer counting, progressive alignment using a new profile function the authors call the log-expectation score, and refinement using tree-dependent restricted partitioning.
Abstract: We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the logexpectation score, and refinement using treedependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5. com/muscle.
37,524 citations
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TL;DR: This version of MAFFT has several new features, including options for adding unaligned sequences into an existing alignment, adjustment of direction in nucleotide alignment, constrained alignment and parallel processing, which were implemented after the previous major update.
Abstract: We report a major update of the MAFFT multiple sequence alignment program. This version has several new features, including options for adding unaligned sequences into an existing alignment, adjustment of direction in nucleotide alignment, constrained alignment and parallel processing, which were implemented after the previous major update. This report shows actual examples to explain how these features work, alone and in combination. Some examples incorrectly aligned by MAFFT are also shown to clarify its limitations. We discuss how to avoid misalignments, and our ongoing efforts to overcome such limitations.
27,771 citations
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
22,269 citations