The molecular dynamics (MD) computer simulation technique is powerful for the investigation of conformational equilibrium properties of biomolecules. In particular, free energy surfaces of the torsion angles (those degrees of freedom from which the geometry mostly depends) allow one to access conformational states, as well as kinetic information, i.e., if the transitions between conformational states occur by simple jumps between wells or if conformational regions close to these states also are populated. The information obtained from MD simulations may depend substantially on the force field employed, and thus, a validation procedure is essential. NMR relaxation data are expected to be highly sensitive to the details of the torsional free energy surface. As a case-study, we consider the disaccharide α-l-Rhap-(1 → 2)-α-l-Rhap-OMe that features only two important torsion angles, ϕ and ψ, which define the interglycosidic orientation of the sugar residues relative to each other, governed mainly by the exo-anomeric effect and steric interactions, respectively. In water, a ψ- state is preferred, whereas in DMSO, it is a ψ+ state, suggesting inherent flexibility at the torsion angle. MD simulations indicated that bistable potentials describe the conformational region well. To test whether a unimodal distribution suffices or if a bimodal distribution better represents molecular conformational preferences, we performed an alchemical morphing of the torsional free energy surface and computed T1, T2, and NOE13C NMR relaxation data that were compared to experimental data. All three NMR observables are substantially affected by the morphing procedure, and the results strongly support a bimodal Boltzmann equilibrium density with a major and a minor conformational state bisected at ψ ≈ 0°, in accord with MD simulations in an explicit solvent.

中文翻译：

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糖苷键的柔性：由13C NMR自旋弛豫推论得出，ψ扭转角在α-L-Rhap-（1→2）-α-L-Rhap-OMe中具有双峰分布。

分子动力学（MD）计算机仿真技术对于研究生物分子的构象平衡特性非常有用。尤其是，扭转角的自由能表面（几何形状主要依赖于这些自由度）允许人们访问构象状态以及动力学信息，即构象状态之间的转换是否通过井间的简单跳跃而发生。如果也填充接近这些状态的构象区域。从MD模拟获得的信息可能主要取决于所采用的力场，因此，验证过程至关重要。预计NMR弛豫数据对扭转自由能表面的细节高度敏感。作为案例研究，我们认为二糖α-1-Rhap-（1→2）-α-1-Rhap-OMe仅具有两个重要的扭转角和ψ，它们定义了糖残基彼此之间的糖苷间取向主要通过外异头作用和空间相互作用。在水中，优选的是ψ-状态，而在DMSO中，它是ψ+状态，表明在扭转角具有固有的柔韧性。MD模拟表明，双稳态电势很好地描述了构象区域。为了测试单峰分布是否足够，或者双峰分布是否更好地代表了分子构象偏好，我们对扭转自由能表面进行了化学变形，并计算了T1，T2和NOE13C NMR弛豫数据，并将其与实验数据进行了比较。