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Prolonged mid-air interaction in virtual reality (VR) causes arm fatigue and discomfort, negatively affecting user experience. Incorporating ergonomic considerations into VR user interface (UI) design typically requires extensive human-in-the-loop evaluation. Although biomechanical models have been used to simulate human behavior in HCI tasks, their application as surrogate users for ergonomic VR UI design remains underexplored. We propose a hierarchical reinforcement learning framework that leverages biomechanical user models to evaluate and optimize VR interfaces for mid-air interaction. A motion agent is trained to perform button-press tasks in VR under sequential conditions, using realistic movement strategies and estimating muscle-level effort via a validated three-compartment control with recovery (3CC-r) fatigue model. The simulated fatigue output serves as feedback for a UI agent that optimizes UI element layout via reinforcement learning (RL) to minimize fatigue. We compare the RL-optimized layout against a manually-designed centered baseline and a Bayesian optimized baseline. Results show that fatigue trends from the biomechanical model align with human user data. Moreover, the RL-optimized layout using simulated fatigue feedback produced significantly lower perceived fatigue in a follow-up human study. We further demonstrate the framework's extensibility via a simulated case study on longer sequential tasks with non-uniform interaction frequencies. To our knowledge, this is the first work using simulated biomechanical muscle fatigue as a direct optimization signal for VR UI layout design. Our findings highlight the potential of biomechanical user models as effective surrogate tools for ergonomic VR interface design, enabling efficient early-stage iteration with less reliance on extensive human participation.