In kinesin walking cycle, NL undergoes a large conformational change from the undocked state to the docked state repeatedly (Fig. To understand the docking mechanism of β10, it is necessary to find out the origin of the strength difference among these backbone HBs at an amino acid level. These backbone HBs, though they are formed in the same way, show big differences in their effective strength. The C-terminal β10 of NL docks to the motor domain through forming four backbone hydrogen bonds (HBs). The NL consists of amino acids that connect kinesin’s motor domain and coiled-coil stalk. Kinesin’s neck linker (NL) docking to the motor domain is the key force generation step of kinesin. The intimate relationship between the effective strength of protein backbone HB and water revealed here should be considered when performing mechanical analysis for protein conformational changes.Ĭonventional kinesin (kinesin-1, here is referred to as kinesin) is a highly processive motor protein, which effectively converts the chemical energy carried by adenosine triphosphate (ATP) into mechanical force and walks hundreds of steps along a microtubule with cargos. In contrast, the backbone HB at the N-terminus of β10 is protected by the surrounding hydrophobic and hydrophilic residues which cooperate positively with the central backbone HB and make this HB highly strong. Along these channels the water molecules can directly attack the backbone HBs and make these HBs relatively weak. The arrangement of the residues in the C-terminal part of β10 results in the existence of the water-attack channels around the backbone HBs in this region. We find that the strength differences of these backbone HBs mainly arise from their relationships with water molecules which are controlled by arranging the surrounding residue sidechains. Using molecular dynamics method, we investigate the stability of the backbone HBs in explicit water environment. The origins of these strength differences are still unclear. These backbone hydrogen bonds show big differences in their effective strength. In this process, NL’s β10 portion forms four backbone hydrogen bonds (HBs) with the motor domain. Such ability to bind biological molecules is an inherent feature of protein structure if combined with appropriate protein sequences, it could provide the non-zero background probability for low-level function that evolution requires for selection to occur.Docking of the kinesin’s neck linker (NL) to the motor domain is the key force-generation process of the kinesin. Thus, backbone hydrogen bonding plays an important role not only in protein structure but also in protein function. These studies also suggest that the packing of secondary structural elements generates the requisite geometry for intermolecular binding. This implies that it is local chain stiffness, even without backbone hydrogen bonding, and compactness that give rise to the likely completeness of the library solved single domain protein structures. Surprisingly, these quasi-spherical random proteins exhibit protein like distributions of virtual bond angles and almost all have a statistically significant structural match to real protein structures. In contrast, the quasi-spherical random proteins, being devoid of secondary structure, have a lower surface to volume ratio and lack ligand binding pockets and intermolecular interaction interfaces. Moreover, these artificial structures have native like ligand binding cavities, and a tiny subset has interfacial geometries consistent with native-like protein– protein interactions and DNA binding. Without any evolutionary selection, the library of artificial structures has similar backbone hydrogen bonding, global shape, surface to volume ratio and statistically significant structural matches to real protein global structures. The intrinsic ability of protein structures to exhibit the geometric features required for molecular function in the absence of evolution is examined in the context of three systems: the reference set of real, single domain protein structures, a library of computationally generated, compact homopolypeptides, artificial structures with protein-like secondary structural elements, and quasi-spherical random proteins packed at the same density as proteins but lacking backbone secondary structure and hydrogen bonding.
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