Free energy calculation of single molecular interaction using Jarzynski's identity method:the case of HIV-1 protease inhibitor system

Jarzynski＇ identity （JI） method was suggested a promising tool for reconstructing free energy landscape of biomolecular interactions in numerical simulations and ex- periments. However, JI method has not yet been well tested in complex systems such as ligand-receptor molecular pairs. In this paper, we applied a huge number of steered molec- ular dynamics （SMD） simulations to dissociate the protease of human immunodeficiency type I virus （HIV-1 protease） and its inhibitors. We showed that because of intrinsic com- plexity of the ligand-receptor system, the energy barrier pre- dicted by JI method at high pulling rates is much higher than experimental results. However, with a slower pulling rate and fewer switch times of simulations, the predictions of JI method can approach to the experiments. These results sug- gested that the JI method is more appropriate for reconstruct- ing free energy landscape using the data taken from experi- ments, since the pulling rates used in experiments are often much slower than those in SMD simulations. Furthermore, we showed that a higher loading stiffness can produce higher precision of calculation of energy landscape because it yields a lower mean value and narrower bandwidth of work distri- bution in SMD simulations.

Design of Implant Prosthesis for Bone Injury Repair Considering Stress Shielding Effect

The failure of bone injury repair surgery is mostly due to the stress shielding effect caused by the difference of elastic modulus between the implant prosthesis and human bone,result-ing in a great damage to patients.To solve this problem,in this study,the influencing factors of the elastic modulus of implant prosthesis were investigated,the relationship between the elastic modulus of the implanted prosthesis and the influencing factors was analyzed,and then a design method of the implant prosthesis to reduce the stress shielding effect by adjusting the unit module to control the elastic modulus was established.This method was used for the biomechanical simula-tion to simulate the displacement and stress distribution between the implant prosthesis and the surrounding bone tissue,and then the reliability of the method was verified.The implant prosthe-sis with an elastic modulus consistent with that of the experimental dog bone was made by this method,and used for the animal experiments.The effects of implant prosthesis with different mod-ulus on the growth of surrounding bone tissue were observed,and at the same time,the reliability of the implant design method and the results of biomechanical simulation were verified.It is con-firmed that this method can effectively reduce the stress concentration of implant prosthesis by more than 15.4%and increase the growth of bone tissue by more than 21%.

Fibula pro-tibia vs standard locking plate fixation in an ankle fracture saw bone model

BACKGROUND Locking plate fixation in osteoporotic ankle fractures may fail due to cut-out or metalwork failure.Fibula pro-tibia fixation was a technique prior to the advent of locking plates that was used to enhance stability in ankle fractures by achieving tri or tetra-cortical fixation.With locking plates,the strength of this fixation construct can be further enhanced.There is lack of evidence currently on the merits of tibiapro-fibula augmented locking plate fixation of unstable ankle fractures.AIM To assess if there is increased strength to failure,in an ankle fracture saw bone model,with a fibula pro-tibia construct when compared with standard locking plate fixation.METHODS Ten osteoporotic saw bones with simulated supination external rotation injuries were used.Five saw bones were fixed with standard locking plates whilst the other 5 saw bones were fixed with locking plates in a fibula pro-tibia construct.The fibula pro-tibia construct involved fixation with 3 consecutive locking screws applied across 3 cortices proximally from the level of the syndesmosis.All fixations were tested in axial external rotation to failure on an electromagnetic test frame(MTS 858 Mini-Bionix test machine,MTS Corp,Eden Praire,MN,United States).Torque at 30 degrees external rotation,failure torque,and external rotation angle at failure were compared between both groups and statistically analyzed.RESULTS The fibula pro-tibia construct demonstrated a statistically higher torque at 30 degrees external rotation(4.421±0.796 N/m vs 1.451±0.467 N/m;t-test P=0.000),as well as maximum torque at failure(5.079±0.694N/m vs 2.299±0.931 N/m;t-test P=0.001)compared to the standard locking plate construct.The fibula pro-tibia construct also had a lower external rotation angle at failure(54.7±14.5 vs 67.7±22.9).CONCLUSION The fibula pro-tibia locking plate construct demonstrates biomechanical superiority to standard locking plates in fixation of unstable ankle fractures in this saw bone model.There is merit in the use of this construct in patients with unstable osteoporotic ankle fractures as it may aid improved clinical outcomes.