Energy Flow Perspective on the Mechanism of the Conformational Dynamics in Biomolecules

Most functional processes of proteins involve significant conformational changes. In those activated processes, the system needs to cross an energy barrier. A comprehensive understanding of activated dynamics is necessary for understanding protein functions. We developed a rigorous method for computing the potential and kinetic energy flows of individual coordinates, which define the energy cost of their movements. Moreover, by introducing the generalized work functional, a fundamental mechanical operator that can characterize the effects of mechanical coupling, we can identify the reaction coordinates that determine the progress of a reaction process. Applying these methods to the isomerization reaction of an alanine dipeptide, we found that a large amount of kinetic energy accumulates in the reaction coordinates before the system starts to cross the activation barrier, which is then used to cover the potential energy cost during barrier crossing. Additionally, we studied the flap opening process of HIV-1 protease, which is essential for substrate binding. Through the energy flow analysis of individual coordinates, we found the extent of energy accumulations strongly correlates with the scale of movements of residues. The coordinates precisely cooperate to form collective modes with high-energy flows and control the reaction dynamics. Our method provides a rigorous scheme to systematically study the contributions of different coordinates to the reactive process and extract the coordinate collectivity from the energy flow perspective, which is fundamentally different from the intuition-guided approaches

The emotional tendencies of 47 perceptual subcategories of traditional settlement cultural landscapes.

The emotional tendencies of 47 perceptual subcategories of traditional settlement cultural landscapes.</p

Semantic networks of traditional settlement cultural landscape perception.

Semantic networks of traditional settlement cultural landscape perception.</p

Research sample list.

The cultural landscape in traditional settlements is an important historical and cultural resource created by human beings in the process of historical evolution, and is an important resource for the development of traditional settlement tourism. This paper selected 21 representative traditional settlements for research using online comments from tourists as data and content analytical methods including high-frequency vocabulary, semantic networks and emotional attitudes to explore the public perspective on the connotations of cultural landscape features in traditional settlements. There are four major findings, showing first that the cultural landscape of traditional settlements contains three core elements. Second, the semantic network relationships of the core elements show a significant central–edge tendency; and third, the emotional perception of cultural landscapes in traditional settlements is generally positive, and there is no significant difference emotionally between each core element. Last, the public’s perception of the cultural connotations of the landscape is seriously insufficient. Based on the research results, planning suggestions and countermeasures for the conservation and utilization of cultural landscapes in traditional settlements are proposed.</div

Element system of cultural landscape perception in traditional settlements.

Element system of cultural landscape perception in traditional settlements.</p

Catalytic Mechanism of Angiotensin-Converting Enzyme and Effects of the Chloride Ion

The angiotensin-converting enzyme (ACE) exhibits critical functions in the conversion of angiotensin I to angiotensin II and the degradation of bradykinin and other vasoactive peptides. As a result, the ACE inhibition has become a promising approach in the treatment of hypertension, heart failure, and diabetic nephropathy. Extending our recent molecular dynamics simulation of the testis ACE in complex with a bona fide substrate molecule, hippuryl-histidyl-leucine, we presented here a detailed investigation of the hydrolytic process and possible influences of the chloride ion on the reaction using a combined quantum mechanical and molecule mechanical method. Similar to carboxypeptidase A and thermolysin, the promoted water mechanism is established for the catalysis of ACE. The E384 residue was found to have the dual function of a general base for activating the water nucleophile and a general acid for facilitating the cleavage of amide C–N bond. Consistent with experimental observations, the chloride ion at the second binding position is found to accelerate the reaction rate presumably due to the long-range electrostatic interactions but has little influence on the overall substrate binding characteristics

Valid data after deleting invalid online comments.

Valid data after deleting invalid online comments.</p

High-frequency vocabulary in traditional settlement culture perception.

High-frequency vocabulary in traditional settlement culture perception.</p

The general emotional tendencies in traditional settlement culture landscape perception.

The general emotional tendencies in traditional settlement culture landscape perception.</p

Original online comment data.

The cultural landscape in traditional settlements is an important historical and cultural resource created by human beings in the process of historical evolution, and is an important resource for the development of traditional settlement tourism. This paper selected 21 representative traditional settlements for research using online comments from tourists as data and content analytical methods including high-frequency vocabulary, semantic networks and emotional attitudes to explore the public perspective on the connotations of cultural landscape features in traditional settlements. There are four major findings, showing first that the cultural landscape of traditional settlements contains three core elements. Second, the semantic network relationships of the core elements show a significant central–edge tendency; and third, the emotional perception of cultural landscapes in traditional settlements is generally positive, and there is no significant difference emotionally between each core element. Last, the public’s perception of the cultural connotations of the landscape is seriously insufficient. Based on the research results, planning suggestions and countermeasures for the conservation and utilization of cultural landscapes in traditional settlements are proposed.</div