Energy Landscape of Aptamer/Protein Complexes Studied by Single‐Molecule Force Spectroscopy

Aptamers are single‐stranded nucleic acid molecules selected in vitro to bind to a variety of target molecules. Aptamers bound to proteins are emerging as a new class of molecules that rival commonly used antibodies in both therapeutic and diagnostic applications. With the increasing application of aptamers as molecular probes for protein recognition, it is important to understand the molecular mechanism of aptamer–protein interaction. Recently, we developed a method of using atomic force microscopy (AFM) to study the single‐molecule rupture force of aptamer/protein complexes. In this work, we investigate further the unbinding dynamics of aptamer/protein complexes and their dissociation‐energy landscape by AFM. The dependence of single‐molecule force on the AFM loading rate was plotted for three aptamer/protein complexes and their dissociation rate constants, and other parameters characterizing their dissociation pathways were obtained. Furthermore, the single‐molecule force spectra of three aptamer/protein complexes were compared to those of the corresponding antibody/protein complexes in the same loading‐rate range. The results revealed two activation barriers and one intermediate state in the unbinding process of aptamer/protein complexes, which is different from the energy landscape of antibody/protein complexes. The results provide new information for the study of aptamer–protein interaction at the molecular level.     

Some mathematical aspects of Anderson localization: boundary effect,multimodality, and bifurcation

Anderson localization is a famous wave phenomenon that describes the absence of diffusion of waves in a disordered medium. Here we generalize the landscape theory of Anderson localization to general elliptic operators and complex boundary conditions using a probabilistic approach, and further investigate some mathematical aspects of Anderson localization that are rarely discussed before. First, we observe that under the Neumann boundary condition, the low energy quantum states are localized on the boundary of the domain with high probability. We provide a detailed explanation of this phenomenon using the concept of extended subregions and obtain an analytical expression of this probability in the one-dimensional case. Second, we find that the quantum states may be localized in multiple different subregions with high probability in the one-dimensional case and we derive an explicit expression of this probability for various boundary conditions. Finally, we examine a bifurcation phenomenon of the localization subregion as the strength of disorder varies. The critical threshold of bifurcation is analytically computed based on a toy model and the dependence of the critical threshold on model parameters is analyzed.     

Multifunctional land‐use value mapping and space type classification: A case study of Puge County,China

Land exhibits diverse functions under the combined influence of natural and human forces. A production–living–ecology functional classification system was constructed by integrating land, ecosystem, and landscape functions. The land functional value was calculated by systematically integrating ecosystem service value assessments. The primary and secondary functions, as well as combinations of different land‐use types, were determined using vertical and horizontal comparison methods. The production–living–ecology ranges were then delineated in Puge County, which is a typical mountain county in China. The production–living–ecology functions identified were well connected with the current land‐use types. The “production–living–ecology” space in Puge County showed obvious multifunctionality and agglomeration. The function identification system proposed in this paper integrated multiple methods, overcame the difficulty of direct quantitative identification of land functions. The methods used to map and quantify land function will enhance our ability to understand and model land system changes and adequately inform policies and planning. Summary for Managers

• The function valuation method constructed in this paper could be used to reflect the multifunctionality and importance of land use and provide guidance and a quantitative basis for regional development planning.
• The spatial classification results provided in this paper could offer a valuable reference for the land management department to scientifically formulate land use planning.
• Under the goal of creating a group‐type urban development pattern and constructing an ecological protection pattern in Puge County, the hotspot analysis results of this paper can provide decision‐making tools and alternative spatial plans.

     

Transiting the molecular potential energy surface along low energy pathways: The TRREAT algorithm

The Transition Rapidly exploring Random Eigenvector Assisted Tree (TRREAT) algorithm is introduced to perform searches along low curvature pathways on a potential energy surface (PES). The method combines local curvature information about the PES with an iterative Rapidly exploring Random Tree algorithm (LaValle, Computer Science Department, Iowa State University, 1998, TR98–11) that quickly searches high‐dimensional spaces for feasible pathways between local minima. Herein, the method is applied to identifying conformational changes of molecular systems using Cartesian coordinates while avoiding a priori definition of collective variables. We analyze the pathway identification problem for alanine dipeptide, cyclohexane and glycine using nonreactive and reactive forcefields. We show how TRREAT‐identified pathways can be used as valuable input guesses for double‐ended methods such as the Nudged Elastic Band when ascertaining transition state energies. This method can be utilized to improve/extend the reaction databases that lie at the core of automatic chemical reaction mechanism generator software currently developed to build kinetic models of chemical reactions. © 2013 Wiley Periodicals, Inc.     

Adaptive lambda square dynamics simulation: An efficient conformational sampling method for biomolecules

A novel, efficient sampling method for biomolecules is proposed. The partial multicanonical molecular dynamics (McMD) was recently developed as a method that improved generalized ensemble (GE) methods to focus sampling only on a part of a system (GEPS); however, it was not tested well. We found that partial McMD did not work well for polylysine decapeptide and gave significantly worse sampling efficiency than a conventional GE. Herein, we elucidate the fundamental reason for this and propose a novel GEPS, adaptive lambda square dynamics (ALSD), which can resolve the problem faced when using partial McMD. We demonstrate that ALSD greatly increases the sampling efficiency over a conventional GE. We believe that ALSD is an effective method and is applicable to the conformational sampling of larger and more complicated biomolecule systems. © 2013 Wiley Periodicals, Inc.     

大型综合医院室外声景观评价影响因素分析——以长沙市中心医院为例

大型综合医院室外本是医患康复疗养、舒缓身心的场所,但并未引起足够的重视,噪声影响严重,声景观较差.该文以长沙市中心医院为例,通过定点实测结合问卷调查的方式,探究影响大型综合医院室外声景观评价结果的因素.结果表明:长沙市中心医院室外声景观整体满意度一般,语义词调查结果整体偏向贬义负值,受访者身份、调查时间和声源构成对声景...     

Structural-Deformation-Energy-Modulation Strategy in a Soft Porous Coordination Polymer with an Interpenetrated Framework

To achieve unique molecular-recognition patterns, a rational control of the flexibility of porous coordination polymers (PCPs) is highly sought, but it remains elusive. From a thermodynamic perspective, the competitive relationship between the structural deformation energy (E_def) of soft PCPs and the guest interaction is key for selective a guest-triggered structural-transformation behavior. Therefore, it is vital to investigate and control E_def to regulate this competition for flexibility control. Driven by these theoretical insights, we demonstrate an E_def-modulation strategy via encoding inter-framework hydrogen bonds into a soft PCP with an interpenetrated structure. As a proof of this concept, the enhanced E_def of PCP enables a selective gate-opening behavior toward CHCl₃ over CH₂Cl₂ by changing the adsorption-energy landscape of the compounds. This study provides a new direction for the design of functional soft porous materials.     

Exhaustive search of the configurational space of heat-shock protein 90 with its inhibitor by multicanonical molecular dynamics based dynamic docking

Multicanonical molecular dynamics based dynamic docking was used to exhaustively search the configurational space of an inhibitor binding to the N-terminal domain of heat-shock protein 90 (Hsp90). The obtained structures at 300 K cover a wide structural ensemble, with the top two clusters ranked by their free energy coinciding with the native binding site. The representative structure of the most stable cluster reproduced the experimental binding configuration, but an interesting conformational change in Hsp90 could be observed. The combined effects of solvation and ligand binding shift the equilibrium from a preferred loop-in conformation in the unbound state to an α-helical one in the bound state for the flexible lid region of Hsp90. Thus, our dynamic docking method is effective at predicting the native binding site while exhaustively sampling a wide configurational space, modulating the protein structure upon binding.     

Insights into the Structure and Energy of DNA Nanoassemblies

Since the pioneering work of Ned Seeman in the early 1980s, the use of the DNA molecule as a construction material experienced a rapid growth and led to the establishment of a new field of science, nowadays called structural DNA nanotechnology. Here, the self-recognition properties of DNA are employed to build micrometer-large molecular objects with nanometer-sized features, thus bridging the nano- to the microscopic world in a programmable fashion. Distinct design strategies and experimental procedures have been developed over the years, enabling the realization of extremely sophisticated structures with a level of control that approaches that of natural macromolecular assemblies. Nevertheless, our understanding of the building process, i.e., what defines the route that goes from the initial mixture of DNA strands to the final intertwined superstructure, is, in some cases, still limited. In this review, we describe the main structural and energetic features of DNA nanoconstructs, from the simple Holliday junction to more complicated DNA architectures, and present the theoretical frameworks that have been formulated until now to explain their self-assembly. Deeper insights into the underlying principles of DNA self-assembly may certainly help us to overcome current experimental challenges and foster the development of original strategies inspired to dissipative and evolutive assembly processes occurring in nature.