Some highly designable protein structures have dented on the surface of their native structures, and are not full compactly folded. According to hydrophobic-polar （HP） model the most designable structures are full c...Some highly designable protein structures have dented on the surface of their native structures, and are not full compactly folded. According to hydrophobic-polar （HP） model the most designable structures are full compactly folded. To investigate the designability of the dented structures, we introduce the hydrogen bond energy in the secondary structures by using the secondary-structure-favored HP model proposed by Ou-yang etc. The result shows that the average designability increases with the strength of the hydrogen bond. The designabilities of the structures with same dented shape increase exponentially with the number of secondary structure sites. The dented structures can have the highest designabilities for a certain value of hydrogen bond energy density.展开更多
Although the advanced 3-dimensional structure measurements provide more and more detailed structures in Protein Data Bank, the simplest 2-dimensional lattice model still looks meaningful because 2-dimensional structur...Although the advanced 3-dimensional structure measurements provide more and more detailed structures in Protein Data Bank, the simplest 2-dimensional lattice model still looks meaningful because 2-dimensional structures play a complementary role with respect to 3-dimensional structures. In this study, the folding structures of delta-hemolysin and its six variants were studied at 2-dimensional lattice, and their amino acid contacts in folding structures were considered according to HP model with the aid of normalized amino acid hydrophobicity index. The results showed that: 1) either delta-hemolysin or each of its variants could find any of its folding structure in one eighth of 1,129,718,145,924 folding structures because of symmetry, which reduces the time required for folding, 2) the impact of pH on folding structures is varying and associated directly with the amino acid sequence itself, 3) the changes in folding structures of variants appeared different case by case, and 4) the assigning of hydrophobicity index to each amino acid was a way to distinguish folding structures at the same native state. This study can help to understand the structure of delta-hemolysin, and such an analysis can shed lights on NP-problem listed in millennium prize because the HP folding in lattice belongs to a sub-problem of NP-problem.展开更多
An understanding of protein folding/unfolding processes has important implications for all biological processes, in- eluding protein degradation, protein translocation, aging, and diseases. All-atom molecular dynamics...An understanding of protein folding/unfolding processes has important implications for all biological processes, in- eluding protein degradation, protein translocation, aging, and diseases. All-atom molecular dynamics （MD） simulations are uniquely suitable for it because of their atomic level resolution and accuracy. However, limited by computational ca- pabilities, nowadays even for small and fast-folding proteins, all-atom MD simulations of protein folding still presents a great challenge. An alternative way is to study unfolding process using MD simulations at high temperature. High temper- ature provides more energy to overcome energetic barriers to unfolding, and information obtained from studying unfolding can shed light on the mechanism of folding. In the present study, a 1000-ns MD simulation at high temperature （500 K） was performed to investigate the unfolding process of a small protein, chicken villin headpiece （HP-35）. To infer the folding mechanism, a Markov state model was also built from our simulation, which maps out six macrostates during the folding/unfolding process as well as critical transitions between them, revealing the folding mechanism unambiguously.展开更多
基金Supported by the Foundation for the Author of National Excellent Doctoral Dissertation of China (200525)the Science and Tech-nology Program of Wuhan City (20067003111-07)
文摘Some highly designable protein structures have dented on the surface of their native structures, and are not full compactly folded. According to hydrophobic-polar （HP） model the most designable structures are full compactly folded. To investigate the designability of the dented structures, we introduce the hydrogen bond energy in the secondary structures by using the secondary-structure-favored HP model proposed by Ou-yang etc. The result shows that the average designability increases with the strength of the hydrogen bond. The designabilities of the structures with same dented shape increase exponentially with the number of secondary structure sites. The dented structures can have the highest designabilities for a certain value of hydrogen bond energy density.
文摘Although the advanced 3-dimensional structure measurements provide more and more detailed structures in Protein Data Bank, the simplest 2-dimensional lattice model still looks meaningful because 2-dimensional structures play a complementary role with respect to 3-dimensional structures. In this study, the folding structures of delta-hemolysin and its six variants were studied at 2-dimensional lattice, and their amino acid contacts in folding structures were considered according to HP model with the aid of normalized amino acid hydrophobicity index. The results showed that: 1) either delta-hemolysin or each of its variants could find any of its folding structure in one eighth of 1,129,718,145,924 folding structures because of symmetry, which reduces the time required for folding, 2) the impact of pH on folding structures is varying and associated directly with the amino acid sequence itself, 3) the changes in folding structures of variants appeared different case by case, and 4) the assigning of hydrophobicity index to each amino acid was a way to distinguish folding structures at the same native state. This study can help to understand the structure of delta-hemolysin, and such an analysis can shed lights on NP-problem listed in millennium prize because the HP folding in lattice belongs to a sub-problem of NP-problem.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11175068 and 11474117)the Self-determined Research Funds of CCNU from the Colleges Basic Research and Operation of MOE,China(Grant No.230-20205170054)
文摘An understanding of protein folding/unfolding processes has important implications for all biological processes, in- eluding protein degradation, protein translocation, aging, and diseases. All-atom molecular dynamics （MD） simulations are uniquely suitable for it because of their atomic level resolution and accuracy. However, limited by computational ca- pabilities, nowadays even for small and fast-folding proteins, all-atom MD simulations of protein folding still presents a great challenge. An alternative way is to study unfolding process using MD simulations at high temperature. High temper- ature provides more energy to overcome energetic barriers to unfolding, and information obtained from studying unfolding can shed light on the mechanism of folding. In the present study, a 1000-ns MD simulation at high temperature （500 K） was performed to investigate the unfolding process of a small protein, chicken villin headpiece （HP-35）. To infer the folding mechanism, a Markov state model was also built from our simulation, which maps out six macrostates during the folding/unfolding process as well as critical transitions between them, revealing the folding mechanism unambiguously.
